Radioimmunotherapy of B-Cell Lymphoma with [131I]Anti-B1 (Anti-CD20) Antibody
Mark S. Kaminski, Kenneth R. Zasadny, Isaac R. Francis, Adam W. Milik, Charles W. Ross, Scott D. Moon, Shelley M. Crawford, Jeanne M. Burgess, Neil A. Petry, Gregory M. Butchko, Stephan D. Glenn, and Richard L. Wahl
Background Many patients with non-Hodgkin's lymphomas are notcured by current therapies, and new approaches to treatmentare needed. As part of an ongoing phase 1 study, we examinedthe effect of radioimmunotherapy with 131I-labeled B-cell-specificanti-CD20 monoclonal antibody in 10 patients with CD20-positiveB-cell lymphomas in whom primary chemotherapy had failed.
Methods and Results Anti-B1 (anti-CD20) mouse monoclonal antibodytrace-labeled with 131I (15 mg containing 5 mCi) was given intravenouslyat approximately one-week intervals: first, without pretreatmentwith unlabeled anti-B1 antibody, to all 10 patients; then withpretreatment with 135 mg of unlabeled antibody, to 8 patients;and then, with pretreatment with 685 mg, to 2 patients. Serialquantitative gamma-camera images and measures of whole-bodyradioactivity were obtained after each tracer dose. All knowndisease sites larger than 2 cm could be imaged. The effect ofa pretreatment dose of unlabeled anti-B1 antibody on targetingof the tumor with the radiolabeled antibody was variable.
The pretreatment dose of unlabeled antibody that produced thehighest ratio of the tumor dose to the whole-body dose in tracerstudies was then used to deliver higher doses of radioactivityfor radioimmunotherapy in nine patients. Three patients receiveddoses designed to deliver 25 cGy to the whole body (two patientstreated twice, six to eight weeks apart), four patients received35 cGy (one patient treated twice), and two patients received45 cGy (one patient treated twice); each dose contained 34 to66 mCi of activity. Six of the nine treated patients had tumorresponses, including patients with bulky or chemotherapy-resistantdisease: four patients had complete remissions, and two hadpartial responses. Three patients had objective responses totracer infusions before they received radioimmunotherapeuticdoses. Of the four patients with complete remissions, one remainedin remission for eight months and the other three continue tohave no disease progression (for 11, 9, and 8 months). Therewas mild or no myelosuppression.
Conclusions Radioimmunotherapy with [131I]anti-B1 antibody isa promising new treatment for lymphoma.
Despite the use of various combined chemotherapeutic regimensfor advanced-stage intermediate- and high-grade lymphomas, roughlyhalf of patients treated do not have a complete remission oreventually have a relapse after a remission. This situationhas not improved noticeably in almost two decades1,2. Treatmentwith standard-dose salvage chemotherapy rarely results in durableremissions and often has serious toxicity. Although the useof high-dose chemotherapy with bone marrow transplantation hasshown promise, not all patients derive long-term benefit fromthis treatment3. Furthermore, a curative treatment for patientswith advanced low-grade lymphoma still remains to be clearlyestablished4. New therapeutic approaches are needed.
Radioimmunotherapy is promising in this regard. In this formof treatment, radioisotope-labeled monoclonal antibodies thatcan recognize and bind tumor-associated antigens are administeredsystemically. Such radiolabeled antibodies may preferentiallytarget radioactivity to tumor sites, sparing normal tissues.Depending on the radioisotope, the radiation emitted from aradiolabeled antibody bound to a tumor cell may also kill nearbymalignant cells that do not express the target antigen at whichthe antibody is directed. Also, the antibody carrying the radioisotopemay affect the tumor either by itself or through indirect mechanismsinvolving interactions with host immune mechanisms.
In this report, we present the results of an ongoing phase 1clinical trial evaluating the tumor targeting, antitumor effects,and toxicity of 131I-labeled anti-B1 antibody, a mouse monoclonalantibody directed against the CD20 B-lymphocyte-associated surface-membraneantigen that is widely expressed by normal and malignant B cells.
Methods
Preparation and Iodination of the Anti-B1 Antibody
The mouse IgG2a monoclonal antibody anti-B1 (anti-CD20), providedby the Coulter Corporation (Hialeah, Fla.), binds to a 35-kdcell-surface phosphoprotein expressed by more than 95 percentof normal B cells isolated from peripheral blood, lymphoid tissues,and bone marrow and more than 90 percent of B-cell lymphomas5.It does not bind T cells, granulocytes, monocytes, erythrocytes,hematopoietic stem cells, or any normal nonhematopoietic tissues5.
The antibody was isolated from serum-free hybridoma supernatantsproduced in cartridge-type bioreactors and purified by ion-exchangechromatography. The resulting preparation was more than 98 percentpure monomeric IgG, sterile and free of pyrogens or adventitiousviruses.
Radioiodination was performed according to the iodogen method6.After passage of the radiolabeled antibody preparation throughan ion-exchange resin column, more than 90 percent of radioactivitywas protein bound as assessed by thin-layer chromatography.The mean specific activities of trace-labeled and radioimmunotherapeutic-dosepreparations were 0.83 and 8.8 mCi per milligram, respectively.A rapid direct cell-binding assay with a one-hour incubationperiod was performed before infusion, to verify preservationof immunoreactivity, as described previously7. Lyophilized targetB cells (Coulter) were reconstituted with 2 percent bovine serumalbumin in phosphate-buffered saline and incubated with radiolabeledantibody under conditions of antigen excess and in the presenceor absence of excess unlabeled anti-B1 antibody. For trace-labeledpreparations, direct cell binding measured 58 percent on average;for therapeutic-dose preparations, the average was 49 percent.These are minimal estimates of immunoreactivity not extrapolatedto conditions of infinite antigen excess8.
All radiolabeled antibody preparations were sterile-filteredand determined to be pyrogen-free by limulus amebocyte lysateassay before injection. The preparation and administration ofthe antibody conformed to federal regulations (Notice of ClaimedInvestigational Exemption for a New Drug).
Selection of Patients
Patients eligible for this study were adults with non-Hodgkin'slymphoma who had relapsed after having received at least onechemotherapy regimen or who had had no response to at leastone regimen, and whose tumor tissue was reactive with eitheranti-B1 antibody (as demonstrated by immunoperoxidase stainingof cryopreserved tumor specimens) or with L26 antibody (as demonstratedby staining of paraffin-embedded tissue); both anti-B1 and L26antibodies specifically bind the CD20 antigen9. The patientswere also required to have iliac-crest bone marrow biopsy samplesshowing that less than 25 percent of the hematopoietic marrowelements were lymphoma cells. They were required to have undergoneno other treatment for at least four weeks and to have an absolutegranulocyte count above 1500 per cubic millimeter and a plateletcount above 100,000 per cubic millimeter at entry, normal hepaticand renal function, no other serious illnesses, a Karnofskyperformance score of at least 60, a life expectancy of at leastthree months, measurable disease, and no human serum antimouseantibodies. All patients gave written informed consent to theirparticipation in the study, which was approved by the institutionalreview board of the University of Michigan.
Antibody Administration
All patients were hospitalized and received anti-B1 antibodytrace-labeled with 131I (15 mg containing 5 mCi) intravenouslyover a 30-minute period. To evaluate the effect of giving unlabeledantibody before radiolabeled antibody on the distribution ofradiolabeled antibody and tumor targeting, a second trace-labeleddose was given approximately one week later, immediately aftera 90-minute infusion of 135 mg of unlabeled anti-B1 antibody.Depending on the availability of antibody and the patient'sclinical status, a third trace-labeled dose was given one totwo weeks later, after a 90-minute infusion of 685 mg of unlabeledantibody.
At least one week after the last trace-labeled dose was given,a dose with higher radioactivity -- the radioimmunotherapeuticdose -- was administered. This dose (15 mg) was given with thepretreatment dose of unlabeled antibody that had previouslyproduced the highest ratio of the tumor dose to the whole-bodydose. The level of radioactivity in the therapeutic dose wasadjusted for each patient so that he or she would receive aspecified dose of whole-body radiation predicted by the resultsof studies with the trace-labeled dose (or doses). Groups ofat least three patients were scheduled to receive escalatingwhole-body doses, which started at 25 cGy and were increasedby 10-cGy increments until a maximal tolerated dose not requiringsupport by bone marrow transplantation was determined. Patientswere eligible for retreatment after eight weeks if they didnot have human antimouse antibodies, had had no dose-limitingtoxic reactions, and had stable disease or tumor regressionwith measurable persistent disease, and if their blood counts,levels of hepatic and renal function, and performance statuswere in the range that was originally required for entry. Retreatmentconsisted of a trace-labeled dose (usually with the same pretreatmentdose of unlabeled antibody used for the previous radioimmunotherapeuticdose) followed one week later by a radioimmunotherapeutic dose(also with the same pretreatment dose of unlabeled antibody)that had been adjusted to deliver the same dose of whole-bodyradiation delivered by the previous radioimmunotherapeutic dose.
Diphenhydramine (50 mg) and acetaminophen (650 mg) were givenorally as premedication one hour before each infusion. Potassiumiodide was given orally (two drops orally three times daily),beginning the day before the first infusion of antibody andcontinuing until 14 days after the last infusion, to inhibituptake of free iodine by the thyroid. Potassium perchlorate(200 mg three times a day for seven days) was given in additionto potassium iodide to patients receiving radioimmunotherapy,beginning the day of the therapeutic infusion. Patients weremonitored for alterations in vital signs and for adverse reactionsevery 15 minutes during infusions. After they received a radioimmunotherapeuticdose, they were isolated in lead-shielded rooms until theirwhole-body radiation level was less than 30 mCi according toionization-chamber measurements.
Dosimetry and Imaging Studies
Serial conjugate anterior and posterior whole-body and spotgamma-camera scans, as well as whole-body radioactivity countsrecorded by sodium iodide scintillation probes, were obtainedone hour after administration of the trace-labeled dose andthen daily for at least five days as previously described10.Post-radioimmunotherapy scanning was begun after the whole-bodyradioactivity level fell to less than 30 mCi. Outlines of theregions of interest were drawn around normal organs, imagedtumors, and appropriate background regions by a computer. Time-activitycurves (the level of radioactivity per gram of tissue plottedagainst time) corresponding to these regions were then generatedand fitted by a least-squares regression program to derive anestimate of cumulative activity. The weights of organs and tumorswere calculated from their volumes recorded on computed tomography(CT) when CT scans were available; otherwise, standard valuesfor organ masses were used11. Dosimetric estimates were thenmade according to the method of the Medical Internal RadiationDose Committee12,13,14,15.
Radioactivity clearance was also determined with a gamma counterin sequential blood samples drawn immediately after infusionand during the following 120 hours. Serum samples were alsoobtained to detect immune-complex formation (measured by high-performanceliquid chromatography and C1q binding assays) within two hoursafter infusion. Urine samples were also collected at designatedintervals after infusion to measure the renal excretion rate.
Gamma-camera scans were interpreted by a single experiencedreader and compared with findings at prestudy physical examinations,body CT scans, and other appropriate radiographic studies todetermine the sensitivity of tumor imaging10.
Evaluation of Toxicity
Toxicity was scored according to the National Cancer Institute'sCommon Toxicity Criteria. Complete blood-cell and platelet countswere obtained immediately after each infusion and then 2, 4,24, 72, and 120 hours after infusion. After the patients' dischargefrom the hospital, blood counts were obtained weekly for atleast eight weeks. Hepatic-enzyme, renal, and electrolyte studieswere performed at least twice during the week after an infusionand once every two weeks for the first two months after discharge.Serum complement levels (C3 and C4) were assayed within twohours after infusion. The peripheral-blood immunophenotype wasdetermined by flow cytometry before and 24 hours after infusionof trace-labeled antibody and one to two months after radioimmunotherapy.Direct staining of Ficoll-Hypaque-separated mononuclear cellswas performed with anti-B1 and anti-CD19 antibodies to identifyB cells and with anti-CD3 antibodies to identify T cells. Otherantibodies used for special studies included anti-CD4, anti-CD8,anti-CD14, and anti-CD45 antibodies and other irrelevant (control)subclass-matched antibodies.
Serum was examined for human antimouse antibodies in samplesobtained before study, weekly until two months after the lastantibody infusion, and monthly thereafter, by means of a sandwichenzyme-linked immunosorbent assay described previously10. Serumimmunoglobulin concentrations were measured and thyroid-functiontests performed before study, one month after radioimmunotherapy,and several months after therapy.
Tumor Response
Tumor response was assessed during the tracer studies beforeradioimmunotherapy, four to six weeks after therapy, and everytwo to three months thereafter. A complete remission was definedas the complete disappearance of all detectable disease fora minimum of four weeks, a partial response as a reduction ofat least 50 percent in the sum of the products of the longestperpendicular diameters of all measurable lesions for a minimumof four weeks, and disease progression as an increase of atleast 25 percent in the diameters or the appearance of new lesions.
Results
The first 10 patients who entered the study are described here,and their characteristics are shown in Table 1. All were men.Half the patients had low-grade lymphomas, and half had intermediate-gradelymphomas. At entry, three patients had high tumor burdens (>500g on CT scanning and physical examination), two had low tumorburdens (<50 g), and five had intermediate tumor burdens(50 to 500 g). Generally, the patients had been heavily treatedwith chemotherapy before entry (mean number of regimens perpatient, 2.7). Half had chemotherapy-resistant disease, indicatedby a response lasting for less than one month after the lastchemotherapeutic treatment.
Table 1. Clinical Characteristics of 10 Patients with B-Cell Lymphoma.
Gamma-camera scans obtained after the administration of trace-labeleddoses of [131I]anti-B1 antibody demonstrated distinct tumorimaging of all known disease sites larger than 2 cm in all patients(i.e., in all of 30 known sites; range, 1 to 9 sites per patient).Lesions 1 to 15 cm in diameter could be detected, includingintrasplenic tumors (Figure 1).
Figure 1. Gamma-Camera Images of Patients with B-Cell Lymphomas after Injection of 131I-Labeled Anti-B1 Antibody.
In Panel A, an anterior view of Patient 9 obtained 120 hours after trace-labeled antibody injection, there are multiple tumors (arrows) 2 to 6 cm in diameter involving the neck, the right axilla, and the iliac, inguinal, and femoral regions. In Panel B, a posterior view of Patient 2 obtained 235 hours after trace-labeled antibody injection, there is distinct focal uptake (arrows) within the spleen consistent with intrasplenic tumor targeting. A CT scan of this patient also demonstrated low-attenuation lesions in the spleen consistent with involvement by lymphoma.
Pretreatment with unlabeled anti-B1 antibody was performed todetermine whether it would enhance the subsequent access ofradiolabeled antibody to tumors through partial or completepresaturation of nonspecific binding sites or reservoirs ofnonmalignant B cells (especially those in the spleen). Suchpretreatment consistently prolonged blood and whole-body clearanceof radioisotope, as compared with the administration of trace-labeledantibody without pretreatment, but its effect on radiolabeled-antibodytargeting of tumor relative to normal tissues was variable.Of the eight patients who received a 135-mg pretreatment doseof unlabeled antibody, two had an increase of more than 20 percentin the tumor-dose: whole-body dose ratio as compared with theratio determined after a previous trace-labeled dose given withoutpretreatment, and three patients had no substantial improvement.The results in the three other patients could not be assessedbecause of overlap of the tumor region with neighboring organsinvolved in free-iodine excretion or decreased tumor volumeafter infusion of trace-labeled antibody. Of the two patientsgiven trace-labeled doses preceded by a 685-mg pretreatmentdose, the results in both were also unassessable because oftumor responses occurring after these infusions.
The calculated doses of radiation delivered to tumors by trace-labeledantibody exceeded those to any uninvolved organ in five of theseven patients in whom radiation delivery could be assessed(Table 2). A dose of up to 24.1 cGy per millicurie (mean ±SE,10.6 ±2.76) could be delivered to the tumor. Featuresunique to the two patients with poorer tumor targeting thatmight account for a suboptimal outcome were gross splenomegaly(750 g) in Patient 1 (the spleen could act as an "antigenicsink" for the labeled antibody) and a high degree of sclerosisin the tumor in Patient 5 (which might limit the access of antibodyto tumor cells).
Table 2. Doses of Radiation Delivered by [131I]Anti-B1 Antibody to Various Sites.
Nine patients received radioimmunotherapeutic doses and couldbe evaluated for response and toxicity (Table 3). One patientdid not receive a therapeutic dose because of rapid tumor progressionand deterioration of physiologic status during tracer studies,which resulted in his becoming ineligible for protocol treatment.Four patients were treated twice (with about two months betweentreatments). An estimated dose of 25 to 45 cGy was deliveredper dose to the whole body, with 34 to 66 mCi per dose. Sixof the nine patients had substantial tumor responses: four patientshad complete remissions, and two had partial responses. Responseswere observed in patients with extensive or bulky disease orchemotherapy-resistant disease (Figure 2). Responses began inthree patients after they received trace-labeled doses, evenbefore they received radioimmunotherapeutic doses. All fourpatients with complete remissions entered remission after theyreceived only one radioimmunotherapeutic dose; a second radioimmunotherapeuticdose resulted in a mixed response in one patient (definite regressionin some tumors and progression in others), no further responsein two, and no change in a residual radiographic abnormalityin one. One complete remission lasted 8 months, and three remissionshave continued without disease progression for 8 to 11 months.Minimal toxicity was observed in all patients with completeevaluations. Most had either reversible grade 1 myelosuppression(leukopenia, thrombocytopenia, or both) four to seven weeksafter radioimmunotherapy, or no toxic reactions. One patienthad a mild rigor and fever during infusion of a radioimmunotherapeuticdose.
Figure 2. Tumor Responses to [131I]Anti-B1 Antibody.
Abdominal CT images of Patient 4 show a large chemotherapy-resistant retroperitoneal mass before study entry (Panel A) and its regression after radioimmunotherapy (Panel B). This response occurred after the first radioimmunotherapeutic dose; no substantive radiographic changes occurred after a second therapeutic dose.
Thoracic CT images of Patient 2 before study entry (Panel C) and six weeks after one radioimmunotherapeutic dose of 45 mCi (Panel D) show regression of chemotherapy-resistant mediastinal and paratracheal lymphadenopathy.
Peripheral-blood flow cytometry revealed that CD20-positiveB cells constituted 2 to 20 percent of circulating mononuclearcells at base line in all patients. The percentage of theseB cells had decreased in most patients by 24 hours after tracerinfusion, with complete depletion of these cells in three patients.CD20 cell counts returned to base line one to three months afterradioimmunotherapy; there was no evidence of increased ratesof infection. The levels of circulating CD3-positive T cellsdid not change significantly. Serum immunoglobulin levels alsodid not change greatly during follow-up in the patients, includingthe five who had low levels before the study. Human antimouseantibodies were detected in two patients 53 and 81 days afterthe first trace-labeled antibody infusion. Hypothyroidism inducedby irradiation of the thyroid has not been observed.
Discussion
The high rate of tumor responses so far in this ongoing study,together with the low level or absence of toxicity, is promising.Four of the six responses observed have been complete and durable.Responses could be achieved with a relatively short course oftreatment in patients with bulky or extensive disease or chemotherapy-resistantdisease. Although the duration of complete remission in someof our patients has not yet been determined, this therapy appearsto offer, at the very least, excellent palliation of diseaseand the potential for repeated treatments if relapse occurs.
These early results appear to be superior to those of previouslypublished trials of therapy based on the use of monoclonal antibodiesfor B-cell lymphoma, but the number of patients in these studiesis small. Trials of unlabeled antibody have demonstrated occasionaltumor responses, generally incomplete and short-lived16,17,18,19,20,21,22.Similarly, tumor responses to antibody-toxin conjugates (immunotoxins)have been infrequent and rarely complete23,24,25. Toxic reactionsto this form of treatment have included hypoalbuminemia, fever,myalgia, rhabdomyolysis, aphasia, and capillary leak. Trialswith radiolabeled B-cell-directed antibodies in which a doserange similar to the range in this trial was used have resultedpredominantly in short partial responses, often accompaniedby substantial myelosuppression10,26,27,28,29. Using doses ofradioactivity almost 10-fold higher than ours, which requiredthat cryopreserved autologous bone marrow be available, Presset al. induced complete remissions in four patients with ananti-CD37 antibody (MB-1) labeled with 131I30. All four patientshad severe myelosuppression, and one required bone marrow reinfusion.Only patients with relatively small tumor burdens were treated.
Several factors may account for the encouraging results of thepresent trial. Anti-B1 antibody appears to be a superior tumor-targetingagent, and the ability to image all tumors larger than 2 cmand even metastases within the spleen (an organ rich in normalB cells) suggests a potential diagnostic role for the radiolabeledantibody. These results compare favorably with those of studiesof the LL2 antibody26 and are superior to those of studies ofthe MB-1 antibody10 and the anti-CD21 antibody OKB731. The radiationdose delivered to tumor by [131I]anti-B1 antibody (10.6 ±2.76cGy per millicurie) appears to be at least double that reportedfor other radiolabeled B-cell antibodies,10,26,27,31 possiblybecause of the specificity of this antibody for B cells. Incontrast to other antigens, CD20 antigen does not modulate afterantibody binding5 (i.e., disappear from the cell surface throughcytosolic internalization or cell-surface-membrane shedding).Internalization of radiolabeled antibody may result in dehalogenationof antibody and subsequent release of free iodine from the cell32;the absence of such a mechanism may allow prolonged retentionof intact radiolabeled antibody by the targeted cell. Bettertumor targeting appeared to translate into improved tumor responsesin our patients, and patients with relatively poorer targetinggenerally did not respond to treatment. This may indicate thatthe tumor responses observed were due to antibody-targeted radiationrather than simply to whole-body irradiation.
In one patient with gross splenomegaly (Patient 1), pretreatmentwith antibody improved the uptake of radiolabeled antibody.When this patient did not receive pretreatment, radioactivitywas localized predominantly in the spleen and no tumor siteswere detectable; but when he received a 135-mg pretreatmentdose, splenic uptake of radioisotope was much reduced and multipletumor sites became detectable. Pretreatment with unlabeled antibodymay help radiolabeled antibody bypass an antigenic sink (suchas the spleen) and allow better access to tumor sites throughcompetition between unlabeled and labeled antibody.
A low dose rate is associated with this form of delivery ofradiation, and data from studies in animals suggest that low-dose-rateirradiation may be more therapeutically effective than instantaneousirradiation delivered fractionally by conventional externalbeam33,34,35. Moreover, low-dose-rate irradiation can induceapoptosis in lymphoid cell lines, and binding of antibody (includinganti-B1 antibody) can be synergistic in the induction of thiseffect36,37.
The antibody moiety of the [131I]anti-B1 conjugate may alsohave antitumor effects. Anti-B1 antibody can induce both antibody-dependent38and complement-dependent cytolysis,39 probably because its Fcportion is of the IgG2a subclass. Also, anti-B1 antibody candirectly induce apoptosis in certain human B-cell-lymphoma celllines (Macklis R: personal communication). We have found thatin nude mice bearing human B-cell xenografts, unlabeled anti-B1antibody can have inhibitory effects on tumor growth comparableto those of the labeled antibody38. Our observation of tumorresponses during tracer studies in the present trial also supportsan antitumor role for the anti-B1 antibody moiety. However,since no patients received only unlabeled antibody and becauseup to 120 cGy could be delivered to tumors by trace-labeleddoses, at present we cannot exclude a targeted-radiation effect.
Thus, it is possible that at least six different antitumor mechanismsmay be working in concert in this form of treatment: antibody-targetedradiation, low-dose-rate irradiation and its incompletely understoodeffects, whole-body irradiation, antibody-dependent cellularcytolysis, complement-dependent cytolysis, and antibody-inducedapoptosis.
This trial is still in its early stages. As escalation of radiationdoses continues, it will be of interest to determine whetherthe frequency and duration of response are enhanced as the maximaltolerated radiation dose is approached. Even at current doselevels, however, this novel, and so far relatively nontoxictreatment appears to have substantial potential as therapy forlymphoma, either by itself or in combination with other treatments.
Supported in part by grants (RO1-CA-56794 [to Dr. Kaminski]and PO1-CA-42768 [to. Dr. Wahl]) from the National Cancer Instituteand a grant (MO1-RR-00042) from the National Institutes of Health.
We are indebted to Jeanette Roesner, Jeffery C. Burke, and SusanFisher for technical assistance, to all the physicians who referredpatients to us for this study, to the nursing staff of the ClinicalResearch Center of the University of Michigan Hospital for theirexcellent care of the patients, and to Pamela Taylor for assistancein the preparation of the manuscript.
Source Information
From the Divisions of Hematology/Oncology (M.S.K., A.W.M., J.M.B.) and Nuclear Medicine (K.R.Z., S.D.M., S.M.C., N.A.P., R.L.W.), Department of Internal Medicine, and the Departments of Radiology (I.R.F., R.L.W.) and Pathology (C.W.R.), University of Michigan, Ann Arbor; and the Coulter Corporation (G.M.B., S.D.G.), Hialeah, Fla.
Address reprint requests to Dr. Kaminski at the Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical Center, 102 Observatory St., Ann Arbor, MI 48109-0724.
References
Gordon LI, Harrington D, Andersen J, et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med 1992;327:1342-1349. [Abstract]
Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993;328:1002-1006. [Free Full Text]
Armitage JO. Bone marrow transplantation in the treatment of patients with lymphoma. Blood 1989;73:1749-1758. [Free Full Text]
DeVita VT Jr, Jaffe ES, Mauch P, Longo DL. Lymphocytic lymphomas. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 3rd ed. Vol. 2. Philadelphia: J.B. Lippincott, 1989:1741-98.
Stashenko P, Nadler LM, Hardy R, Schlossman SF. Characterization of a human B lymphocyte-specific antigen. J Immunol 1980;125:1678-1685. [Abstract]
Fraker PJ, Speck JC Jr. Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun 1978;80:849-857. [CrossRef][Medline]
Wahl RL, Wissing JR, del Rosario R, Zasadny KR. Inhibition of autoradiolysis of radiolabeled monoclonal antibodies by cryopreservation. J Nucl Med 1990;31:84-89. [Free Full Text]
Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA Jr. Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 1984;72:77-89. [CrossRef][Medline]
Mason DY, Comans-Bitter WM, Cordell JL, Verhoeven MA, van Dongen JJ. Antibody L26 recognizes an intracellular epitope on the B-cell-associated CD20 antigen. Am J Pathol 1990;136:1215-1222. [Abstract]
Kaminski MS, Fig LM, Zasadny KR, et al. Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma. J Clin Oncol 1992;10:1696-1711. [Free Full Text]
International Commission on Radiological Protection. Report of the Task Group on Reference Man. Oxford, England: Pergamon Press, 1975.
Ellet WH, Humes RM. Absorbed fractions for small volumes containing photon-emitting radioactivity. NM/MIRD pamphlet no. 8. New York: Society of Nuclear Medicine.
Dillman LT, Von der Lage FC. Radionuclide decay schemes and nuclear parameters for use in radiation-dose estimation. NM/MIRD pamphlet no. 10. New York: Society of Nuclear Medicine.
Snyder WS, Ford MR, Warner GG, Watson SB. "S," absorbed dose per unit cumulated activity for selected radionuclides and organs. NM/MIRD pamphlet no. 11. New York: Society of Nuclear Medicine.
Watson E, Stabin M, Wesley E. MIRDOSE. 2nd ed. Oak Ridge, Tenn.: Associated Universities, 1984.
Nadler LM, Stashenko P, Hardy R, et al. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res 1980;40:3147-3154. [Free Full Text]
Meeker TC, Lowder J, Maloney DG, et al. A clinical trial of anti-idiotype therapy for B cell malignancy. Blood 1985;65:1349-1363. [Free Full Text]
Brown SL, Miller RA, Horning SJ, et al. Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon. Blood 1989;73:651-661. [Free Full Text]
Stevenson GT, Glennie MJ, Hamblin TJ, Lane AC, Stevenson FK. Problems and prospects in the use of lymphoma idiotypes as therapeutic targets. Int J Cancer Suppl 1988;3:9-12. [Medline]
Press OW, Appelbaum F, Ledbetter JA, et al. Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 1987;69:584-591. [Free Full Text]
Hale G, Dyer MJS, Clark MR, et al. Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H. Lancet 1988;2:1394-1399. [Medline]
Dyer MJS, Hale G, Hayhoe FGJ, Waldmann H. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood 1989;73:1431-1439. [Free Full Text]
Vitetta ES, Stone M, Amlot P, et al. Phase I immunotoxin trial in patients with B-cell lymphoma. Cancer Res 1991;51:4052-4058. [Free Full Text]
Grossbard ML, Freedman AS, Ritz J, et al. Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion. Blood 1992;79:576-585. [Free Full Text]
Grossbard ML, Lambert JM, Goldmacher VS, et al. Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J Clin Oncol 1993;11:726-737. [Abstract]
Goldenberg DM, Horowitz JA, Sharkey RM, et al. Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody. J Clin Oncol 1991;9:548-564. [Abstract]
DeNardo SJ, DeNardo GL, O'Grady LF, et al. Treatment of B cell malignancies with 131I Lym-1 monoclonal antibodies. Int J Cancer Suppl 1988;3:96-101. [Medline]
DeNardo S, DeNardo G, O'Grady L, et al. Pilot studies of radioimmunotherapy of B cell lymphoma and leukemia using 131I Lym-1 monoclonal antibody. Antibodies Immunoconjugates Radiopharm 1988;1:17-33.
DeNardo GL, DeNardo SJ, O'Grady LF, Levy NB, Adams GP, Mills SL. Fractionated radioimmunotherapy of B-cell malignancies with 131I Lym-1. Cancer Res 1990;50:Suppl:1014S-1016S. [Medline]
Press OW, Eary JF, Badger CC, et al. Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol 1989;7:1027-1038. [Abstract]
Scheinberg DA, Straus DJ, Yeh SD, et al. A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression. J Clin Oncol 1990;8:792-803. [Abstract]
Press OW, Farr AG, Borroz KI, Anderson SK, Martin PJ. Endocytosis and degradation of monoclonal antibodies targeting human B-cell malignancies. Cancer Res 1989;49:4906-4912. [Free Full Text]
Wessels BW, Vessella RL, Palme DF II, et al. Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts. Int J Radiat Oncol Biol Phys 1989;17:1257-1263. [Medline]
Buchsbaum DJ, ten Haken RK, Heidorn DB, et al. A comparison of 131I-labeled monoclonal antibody 17-1A treatment to external beam irradiation on the growth of LS174T human colon carcinoma xenografts. Int J Radiat Oncol Biol Phys 1990;18:1033-1041. [Medline]
Knox SJ, Levy R, Miller RA, et al. Determinants of the antitumor effect of radiolabeled monoclonal antibodies. Cancer Res 1990;50:4935-4940. [Free Full Text]
Macklis RM, Lin JY, Beresford B, Atcher RW, Hines JJ, Humm JL. Cellular kinetics, dosimetry, and radiobiology of alpha-particle radioimmunotherapy: induction of apoptosis. Radiat Res 1992;130:220-226. [Medline]
Macklis RM, Palayoor S, Chin L, et al. Induction of programmed cell death in malignant lymphomas after radioimmunotherapy. Antibodies Immunoconjugates Radiopharm 1992;5:339. abstract.
Buchsbaum DJ, Wahl RL, Normolle DP, Kaminski MS. Therapy with unlabeled and 131-I-labeled pan-B-cell monoclonal antibodies in nude mice bearing Raji Burkitt's lymphoma xenografts. Cancer Res 1992;52:6476-6481. [Free Full Text]
Bast RC Jr, Ritz J, Lipton JM, et al. Elimination of leukemic cells from human bone marrow using monoclonal antibody and complement. Cancer Res 1983;43:1389-1394. [Free Full Text]
Press, O. W.
(2008). Evidence Mounts for the Efficacy of Radioimmunotherapy for B-Cell Lymphomas. JCO
26: 5147-5150
[Full Text]
Gopal, A. K., Press, O. W., Wilbur, S. M., Maloney, D. G., Pagel, J. M.
(2008). Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab. Blood
112: 830-835
[Abstract][Full Text]
Meyer zum Buschenfelde, C., Feuerstacke, Y., Gotze, K. S., Scholze, K., Peschel, C.
(2008). GM1 Expression of Non-Hodgkin's Lymphoma Determines Susceptibility to Rituximab Treatment. Cancer Res.
68: 5414-5422
[Abstract][Full Text]
Buchegger, F., Press, O. W., Delaloye, A. B., Ketterer, N.
(2008). Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma. The Oncologist
13: 657-667
[Abstract][Full Text]
Kapadia, N. S., Engles, J. M., Wahl, R. L.
(2008). In Vitro Evaluation of Radioprotective and Radiosensitizing Effects of Rituximab. JNM
49: 674-678
[Abstract][Full Text]
Bodet-Milin, C., Kraeber-Bodere, F., Dupas, B., Morschhauser, F., Gastinne, T., Le Gouill, S., Campion, L., Harousseau, J.-L., Wegener, W. A., Goldenberg, D. M., Huglo, D.
(2008). Evaluation of response to fractionated radioimmunotherapy with 90Y-epratuzumab in non-Hodgkin's lymphoma by 18F-fluorodeoxyglucose positron emission tomography. haematol
93: 390-397
[Abstract][Full Text]
Jacene, H. A., Filice, R., Kasecamp, W., Wahl, R. L.
(2007). Comparison of 90Y-Ibritumomab Tiuxetan and 131I-Tositumomab in Clinical Practice. JNM
48: 1767-1776
[Abstract][Full Text]
Leahy, M. F., Seymour, J. F., Hicks, R. J., Turner, J. H.
(2006). Multicenter Phase II Clinical Study of Iodine-131-Rituximab Radioimmunotherapy in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma. JCO
24: 4418-4425
[Abstract][Full Text]
Sharkey, R. M., Goldenberg, D. M.
(2006). Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates. CA Cancer J Clin
56: 226-243
[Abstract][Full Text]
Hamaguchi, Y., Xiu, Y., Komura, K., Nimmerjahn, F., Tedder, T. F.
(2006). Antibody isotype-specific engagement of Fc{gamma} receptors regulates B lymphocyte depletion during CD20 immunotherapy. JEM
203: 743-753
[Abstract][Full Text]
Pagel, J. M., Appelbaum, F. R., Eary, J. F., Rajendran, J., Fisher, D. R., Gooley, T., Ruffner, K., Nemecek, E., Sickle, E., Durack, L., Carreras, J., Horowitz, M. M., Press, O. W., Gopal, A. K., Martin, P. J., Bernstein, I. D., Matthews, D. C.
(2006). 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood
107: 2184-2191
[Abstract][Full Text]
Fisher, R. I., Kaminski, M. S., Wahl, R. L., Knox, S. J., Zelenetz, A. D., Vose, J. M., Leonard, J. P., Kroll, S., Goldsmith, S. J., Coleman, M.
(2005). Tositumomab and Iodine-131 Tositumomab Produces Durable Complete Remissions in a Subset of Heavily Pretreated Patients With Low-Grade and Transformed Non-Hodgkin's Lymphomas. JCO
23: 7565-7573
[Abstract][Full Text]
Scott, A. M., Lee, F.-T., Jones, R., Hopkins, W., MacGregor, D., Cebon, J. S., Hannah, A., Chong, G., U, P., Papenfuss, A., Rigopoulos, A., Sturrock, S., Murphy, R., Wirth, V., Murone, C., Smyth, F. E., Knight, S., Welt, S., Ritter, G., Richards, E., Nice, E. C., Burgess, A. W., Old, L. J.
(2005). A Phase I Trial of Humanized Monoclonal Antibody A33 in Patients with Colorectal Carcinoma: Biodistribution, Pharmacokinetics, and Quantitative Tumor Uptake. Clin. Cancer Res.
11: 4810-4817
[Abstract][Full Text]
Bennett, J. M., Kaminski, M. S., Leonard, J. P., Vose, J. M., Zelenetz, A. D., Knox, S. J., Horning, S., Press, O. W., Radford, J. A., Kroll, S. M., Capizzi, R. L.
(2005). Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab. Blood
105: 4576-4582
[Abstract][Full Text]
Shen, S., DeNardo, S. J., Richman, C. M., Yuan, A., Siantar, C. H., O'Donnell, R. T., Kroger, L. A., DeNardo, G. L.
(2005). Planning Time for Peripheral Blood Stem Cell Infusion After High-Dose Targeted Radionuclide Therapy Using Dosimetry. JNM
46: 1034-1041
[Abstract][Full Text]
Shen, S., Forero, A., LoBuglio, A. F., Breitz, H., Khazaeli, M.B., Fisher, D. R., Wang, W., Meredith, R. F.
(2005). Patient-Specific Dosimetry of Pretargeted Radioimmunotherapy Using CC49 Fusion Protein in Patients with Gastrointestinal Malignancies. JNM
46: 642-651
[Abstract][Full Text]
Hamaguchi, Y., Uchida, J., Cain, D. W., Venturi, G. M., Poe, J. C., Haas, K. M., Tedder, T. F.
(2005). The Peritoneal Cavity Provides a Protective Niche for B1 and Conventional B Lymphocytes during Anti-CD20 Immunotherapy in Mice. J. Immunol.
174: 4389-4399
[Abstract][Full Text]
Kaminski, M. S., Tuck, M., Estes, J., Kolstad, A., Ross, C. W., Zasadny, K., Regan, D., Kison, P., Fisher, S., Kroll, S., Wahl, R. L.
(2005). 131I-Tositumomab Therapy as Initial Treatment for Follicular Lymphoma. NEJM
352: 441-449
[Abstract][Full Text]
Horning, S. J., Younes, A., Jain, V., Kroll, S., Lucas, J., Podoloff, D., Goris, M.
(2005). Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab. JCO
23: 712-719
[Abstract][Full Text]
Palomba, M. L., Roberts, W. K., Dao, T., Manukian, G., Guevara-Patino, J. A., Wolchok, J. D., Scheinberg, D. A., Houghton, A. N.
(2005). CD8+ T-Cell-Dependent Immunity Following Xenogeneic DNA Immunization against CD20 in a Tumor Challenge Model of B-Cell Lymphoma. Clin. Cancer Res.
11: 370-379
[Abstract][Full Text]
Larson, S. M., Krenning, E. P.
(2005). A Pragmatic Perspective on Molecular Targeted Radionuclide Therapy. JNM
46: 1S-3S
[Full Text]
Sharkey, R. M., Goldenberg, D. M.
(2005). Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies. JNM
46: 115S-127S
[Abstract][Full Text]
Wahl, R. L.
(2005). Tositumomab and 131I Therapy in Non-Hodgkin's Lymphoma. JNM
46: 128S-140S
[Abstract][Full Text]
Davis, T. A., Kaminski, M. S., Leonard, J. P., Hsu, F. J., Wilkinson, M., Zelenetz, A., Wahl, R. L., Kroll, S., Coleman, M., Goris, M., Levy, R., Knox, S. J.
(2004). The Radioisotope Contributes Significantly to the Activity of Radioimmunotherapy. Clin. Cancer Res.
10: 7792-7798
[Abstract][Full Text]
Schaffland, A. O., Buchegger, F., Kosinski, M., Antonescu, C., Paschoud, C., Grannavel, C., Pellikka, R., Delaloye, A. B.
(2004). 131I-Rituximab: Relationship Between Immunoreactivity and Specific Activity. JNM
45: 1784-1790
[Abstract][Full Text]
Adams, G. P., Shaller, C. C., Dadachova, E., Simmons, H. H., Horak, E. M., Tesfaye, A., Klein-Szanto, A. J. P., Marks, J. D., Brechbiel, M. W., Weiner, L. M.
(2004). A Single Treatment of Yttrium-90-labeled CHX-A''-C6.5 Diabody Inhibits the Growth of Established Human Tumor Xenografts in Immunodeficient Mice. Cancer Res.
64: 6200-6206
[Abstract][Full Text]
Uchida, J., Hamaguchi, Y., Oliver, J. A., Ravetch, J. V., Poe, J. C., Haas, K. M., Tedder, T. F.
(2004). The Innate Mononuclear Phagocyte Network Depletes B Lymphocytes through Fc Receptor-dependent Mechanisms during Anti-CD20 Antibody Immunotherapy. JEM
199: 1659-1669
[Abstract][Full Text]
Du, Y., Honeychurch, J., Cragg, M. S., Bayne, M., Glennie, M. J., Johnson, P. W. M., Illidge, T. M.
(2004). Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy. Blood
103: 1485-1494
[Abstract][Full Text]
Uchida, J., Lee, Y., Hasegawa, M., Liang, Y., Bradney, A., Oliver, J. A., Bowen, K., Steeber, D. A., Haas, K. M., Poe, J. C., Tedder, T. F.
(2004). Mouse CD20 expression and function. Int Immunol
16: 119-129
[Abstract][Full Text]
Sharkey, R. M., Brenner, A., Burton, J., Hajjar, G., Toder, S. P., Alavi, A., Matthies, A., Tsai, D. E., Schuster, S. J., Stadtmauer, E. A., Czuczman, M. S., Lamonica, D., Kraeber-Bodere, F., Mahe, B., Chatal, J.-F., Rogatko, A., Mardirrosian, G., Goldenberg, D. M.
(2003). Radioimmunotherapy of Non-Hodgkin's Lymphoma with 90Y-DOTA Humanized Anti-CD22 IgG (90Y-Epratuzumab): Do Tumor Targeting and Dosimetry Predict Therapeutic Response?. JNM
44: 2000-2018
[Abstract][Full Text]
Wong, J. Y. C., Shibata, S., Williams, L. E., Kwok, C. S., Liu, A., Chu, D. Z., Yamauchi, D. M., Wilczynski, S., Ikle, D. N., Wu, A. M., Yazaki, P. J., Shively, J. E., Doroshow, J. H., Raubitschek, A. A.
(2003). A Phase I Trial of 90Y-Anti-Carcinoembryonic Antigen Chimeric T84.66 Radioimmunotherapy with 5-Fluorouracil in Patients with Metastatic Colorectal Cancer. Clin. Cancer Res.
9: 5842-5852
[Abstract][Full Text]
Gopal, A. K., Gooley, T. A., Maloney, D. G., Petersdorf, S. H., Eary, J. F., Rajendran, J. G., Bush, S. A., Durack, L. D., Golden, J., Martin, P. J., Matthews, D. C., Appelbaum, F. R., Bernstein, I. D., Press, O. W.
(2003). High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis. Blood
102: 2351-2357
[Abstract][Full Text]
DeNardo, G. L., Mirick, G. R., Kroger, L. A., Bradt, B. M., Lamborn, K. R., DeNardo, S. J.
(2003). Characterization of Human IgG Antimouse Antibody in Patients with B-Cell Malignancies. Clin. Cancer Res.
9: 4013S-4021
[Abstract][Full Text]
Tuscano, J. M., O'Donnell, R. T., Miers, L. A., Kroger, L. A., Kukis, D. L., Lamborn, K. R., Tedder, T. F., DeNardo, G. L.
(2003). Anti-CD22 ligand-blocking antibody HB22.7 has independent lymphomacidal properties and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma xenografts. Blood
101: 3641-3647
[Abstract][Full Text]
Zhang, M., Zhang, Z., Garmestani, K., Schultz, J., Axworthy, D. B., Goldman, C. K., Brechbiel, M. W., Carrasquillo, J. A., Waldmann, T. A.
(2003). Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts. Proc. Natl. Acad. Sci. USA
100: 1891-1895
[Abstract][Full Text]
Sgouros, G., Squeri, S., Ballangrud, A. M., Kolbert, K. S., Teitcher, J. B., Panageas, K. S., Finn, R. D., Divgi, C. R., Larson, S. M., Zelenetz, A. D.
(2003). Patient-Specific, 3-Dimensional Dosimetry in Non-Hodgkin's Lymphoma Patients Treated with 131I-anti-B1 Antibody: Assessment of Tumor Dose-Response. JNM
44: 260-268
[Abstract][Full Text]
Cheson, B. D.
(2003). Radioimmunotherapy of non-Hodgkin lymphomas. Blood
101: 391-398
[Abstract][Full Text]
Zanzonico, P. B.
(2002). Model-Based Versus Patient-Specific Dosimetry: Blurring the Lines. JNM
43: 1665-1666
[Full Text]
Alain, T., Hirasawa, K., Pon, K. J., Nishikawa, S. G., Urbanski, S. J., Auer, Y., Luider, J., Martin, A., Johnston, R. N., Janowska-Wieczorek, A., Lee, P. W. K., Kossakowska, A. E.
(2002). Reovirus therapy of lymphoid malignancies. Blood
100: 4146-4153
[Abstract][Full Text]
Juweid, M. E.
(2002). Radioimmunotherapy of B-Cell Non-Hodgkin's Lymphoma: From Clinical Trials to Clinical Practice. JNM
43: 1507-1529
[Abstract][Full Text]
Witzig, T. E., Gordon, L. I., Cabanillas, F., Czuczman, M. S., Emmanouilides, C., Joyce, R., Pohlman, B. L., Bartlett, N. L., Wiseman, G. A., Padre, N., Grillo-Lopez, A. J., Multani, P., White, C. A.
(2002). Randomized Controlled Trial of Yttrium-90-Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin's Lymphoma. JCO
20: 2453-2463
[Abstract][Full Text]
Kaminski, M. S., Zelenetz, A. D., Press, O. W., Saleh, M., Leonard, J., Fehrenbacher, L., Lister, T. A., Stagg, R. J., Tidmarsh, G. F., Kroll, S., Wahl, R. L., Knox, S. J., Vose, J. M.
(2001). Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade B-Cell Non-Hodgkin's Lymphomas. JCO
19: 3918-3928
[Abstract][Full Text]
Clarke, S E M
(2001). Advances in radionuclide imaging: radionuclide imaging as a guide to therapy. Imaging
13: 171-184
[Abstract][Full Text]
Schnipper, L. E., Strom, T. B.
(2001). A Magic Bullet for Cancer -- How Near and How Far?. NEJM
345: 283-284
[Full Text]
Rutar, F. J., Augustine, S. C., Colcher, D., Siegel, J. A., Jacobson, D. A., Tempero, M. A., Dukat, V. J., Hohenstein, M. A., Gobar, L. S., Vose, J. M.
(2001). Outpatient Treatment with 131I-Anti-B1 Antibody: Radiation Exposure to Family Members. JNM
42: 907-915
[Abstract][Full Text]
McCall, A. M., Shahied, L., Amoroso, A. R., Horak, E. M., Simmons, H. H., Nielson, U., Adams, G. P., Schier, R., Marks, J. D., Weiner, L. M.
(2001). Increasing the Affinity for Tumor Antigen Enhances Bispecific Antibody Cytotoxicity. J. Immunol.
166: 6112-6117
[Abstract][Full Text]
Ballangrud, A. M., Yang, W.-H., Charlton, D. E., McDevitt, M. R., Hamacher, K. A., Panageas, K. S., Ma, D., Bander, N. H., Scheinberg, D. A., Sgouros, G.
(2001). Response of LNCaP Spheroids after Treatment with an {{alpha}}-Particle Emitter (213Bi)-labeled Anti-Prostate-specific Membrane Antigen Antibody (J591). Cancer Res.
61: 2008-2014
[Abstract][Full Text]
Goel, A., Augustine, S., Baranowska-Kortylewicz, J., Colcher, D., Booth, B. J. M., Pavlinkova, G., Tempero, M., Batra, S. K.
(2001). Single-Dose versus Fractionated Radioimmunotherapy of Human Colon Carcinoma Xenografts Using 131I-labeled Multivalent CC49 Single-chain Fvs. Clin. Cancer Res.
7: 175-184
[Abstract][Full Text]
Press, O. W., Leonard, J. P., Coiffier, B., Levy, R., Timmerman, J.
(2001). Immunotherapy of Non-Hodgkin's Lymphomas. ASH Education Book
2001: 221-240
[Abstract][Full Text]
Wong, J. Y. C., Chu, D. Z., Yamauchi, D. M., Williams, L. E., Liu, A., Wilczynski, S., Wu, A. M., Shively, J. E., Doroshow, J. H., Raubitschek, A. A.
(2000). A Phase I Radioimmunotherapy Trial Evaluating 90Yttrium-labeled Anti-Carcinoembryonic Antigen (CEA) Chimeric T84.66 in Patients with Metastatic CEA-producing Malignancies. Clin. Cancer Res.
6: 3855-3863
[Abstract][Full Text]
Hainsworth, J. D.
(2000). Monoclonal Antibody Therapy in Lymphoid Malignancies. The Oncologist
5: 376-384
[Abstract][Full Text]
Kaminski, M. S., Estes, J., Zasadny, K. R., Francis, I. R., Ross, C. W., Tuck, M., Regan, D., Fisher, S., Gutierrez, J., Kroll, S., Stagg, R., Tidmarsh, G., Wahl, R. L.
(2000). Radioimmunotherapy with iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood
96: 1259-1266
[Abstract][Full Text]
Pai-Scherf, L. H., Carrasquillo, J. A., Paik, C., Gansow, O., Whatley, M., Pearson, D., Webber, K., Hamilton, M., Allegra, C., Brechbiel, M., Willingham, M. C., Pastan, I.
(2000). Imaging and Phase I Study of 111In- and 90Y-labeled Anti-LewisY Monoclonal Antibody B3. Clin. Cancer Res.
6: 1720-1730
[Abstract][Full Text]
Axworthy, D. B., Reno, J. M., Hylarides, M. D., Mallett, R. W., Theodore, L. J., Gustavson, L. M., Su, F.-M., Hobson, L. J., Beaumier, P. L., Fritzberg, A. R.
(2000). Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity. Proc. Natl. Acad. Sci. USA
97: 1802-1807
[Abstract][Full Text]
Apostolidis, J., Gupta, R. K., Grenzelias, D., Johnson, P. W. M., Pappa, V. I., Summers, K. E., Salam, A., Adams, K., Norton, A. J., Amess, J. A. L., Matthews, J., Bradburn, M., Lister, T. A., Rohatiner, A. Z. S.
(2000). High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up. JCO
18: 527-527
[Abstract][Full Text]
Witzig, T. E., White, C. A., Wiseman, G. A., Gordon, L. I., Emmanouilides, C., Raubitschek, A., Janakiraman, N., Gutheil, J., Schilder, R. J., Spies, S., Silverman, D. H.S., Parker, E., Grillo-Lopez, A. J.
(1999). Phase I/II Trial of IDEC-Y2B8 Radioimmunotherapy for Treatment of Relapsed or Refractory CD20+ B-Cell Non-Hodgkin's Lymphoma. JCO
17: 3793-3803
[Abstract][Full Text]
Freedman, A. S., Neuberg, D., Mauch, P., Soiffer, R. J., Anderson, K. C., Fisher, D. C., Schlossman, R., Alyea, E. P., Takvorian, T., Jallow, H., Kuhlman, C., Ritz, J., Nadler, L. M., Gribben, J. G.
(1999). Long-Term Follow-Up of Autologous Bone Marrow Transplantation in Patients With Relapsed Follicular Lymphoma. Blood
94: 3325-3333
[Abstract][Full Text]
Matthews, D. C., Appelbaum, F. R., Eary, J. F., Fisher, D. R., Durack, L. D., Hui, T. E., Martin, P. J., Mitchell, D., Press, O. W., Storb, R., Bernstein, I. D.
(1999). Phase I Study of 131I-Anti-CD45 Antibody Plus Cyclophosphamide and Total Body Irradiation for Advanced Acute Leukemia and Myelodysplastic Syndrome. Blood
94: 1237-1247
[Abstract][Full Text]
Illidge, T. M., Cragg, M. S., McBride, H. M., French, R. R., Glennie, M. J.
(1999). The Importance of Antibody-Specificity in Determining Successful Radioimmunotherapy of B-Cell Lymphoma. Blood
94: 233-243
[Abstract][Full Text]
Behr, T. M., Behe, M., Stabin, M. G., Wehrmann, E., Apostolidis, C., Molinet, R., Strutz, F., Fayyazi, A., Wieland, E., Gratz, S., Koch, L., Goldenberg, D. M., Becker, W.
(1999). High-Linear Energy Transfer (LET) {{alpha}} versus Low-LET {beta} Emitters in Radioimmunotherapy of Solid Tumors: Therapeutic Efficacy and Dose-limiting Toxicity of 213Bi- versus 90Y-labeled CO17-1A Fab' Fragments in a Human Colonic Cancer Model. Cancer Res.
59: 2635-2643
[Abstract][Full Text]
Ridgway, J. B. B., Ng, E., Kern, J. A., Lee, J., Brush, J., Goddard, A., Carter, P.
(1999). Identification of a Human Anti-CD55 Single-Chain Fv by Subtractive Panning of a Phage Library Using Tumor and Nontumor Cell Lines. Cancer Res.
59: 2718-2723
[Abstract][Full Text]
Kuan, C.-T., Reist, C. J., Foulon, C. F., Lorimer, I. A. J., Archer, G., Pegram, C. N., Pastan, I., Zalutsky, M. R., Bigner, D. D.
(1999). 125I-labeled Anti-Epidermal Growth Factor Receptor-vIII Single-Chain Fv Exhibits Specific and High-Level Targeting of Glioma Xenografts. Clin. Cancer Res.
5: 1539-1549
[Abstract][Full Text]
Shan, D., Press, O. W., Tsu, T. T., Hayden, M. S., Ledbetter, J. A.
(1999). Characterization of scFv-Ig Constructs Generated from the Anti-CD20 mAb 1F5 Using Linker Peptides of Varying Lengths. J. Immunol.
162: 6589-6595
[Abstract][Full Text]
Shan, D., Ledbetter, J. A., Press, O. W.
(1998). Apoptosis of Malignant Human B Cells by Ligation of CD20 With Monoclonal Antibodies. Blood
91: 1644-1652
[Abstract][Full Text]
Maloney, D. G., Grillo-Lopez, A. J., White, C. A., Bodkin, D., Schilder, R. J., Neidhart, J. A., Janakiraman, N., Foon, K. A., Liles, T.-M., Dallaire, B. K., Wey, K., Royston, I., Davis, T., Levy, R.
(1997). IDEC-C2B8 (Rituximab) Anti-CD20 Monoclonal Antibody Therapy in Patients With Relapsed Low-Grade Non-Hodgkin's Lymphoma. Blood
90: 2188-2195
[Abstract][Full Text]
Gidlof, C., Dohlsten, M., Lando, P., Kalland, T., Sundstrom, C., Totterman, T. H.
(1997). A Superantigen-Antibody Fusion Protein for T-Cell Immunotherapy of Human B-Lineage Malignancies. Blood
89: 2089-2097
[Abstract][Full Text]
Vose, J. M.
(1995). Treatment for Non-Hodgkin's Lymphoma in Relapse -- What Are the Alternatives?. NEJM
333: 1565-1566
[Full Text]
Press, O. W., Eary, J. F., Appelbaum, F. R., Martin, P. J., Badger, C. C., Nelp, W. B., Glenn, S., Butchko, G., Fisher, D., Porter, B., Matthews, D. C., Fisher, L. D., Bernstein, I. D.
(1993). Radiolabeled-Antibody Therapy of B-Cell Lymphoma with Autologous Bone Marrow Support. NEJM
329: 1219-1224
[Abstract][Full Text]
Bast, R. C.
(1993). Progress in Radioimmunotherapy. NEJM
329: 1266-1268
[Full Text]
Previous
