Abstract
The ability of an α-emitter conjugated to a chimaeric anti-CD20 monoclonal antibody to kill selectively human B-lymphoma cells in vitro is reported. Two B-lymphoma cell lines RAEL and K422, and normal haematopoietic progenitor cells from human bone marrow aspirates were incubated with211At-rituximab (Rituxan® or MabThera™) and plated in clonogenic assays for survival analyses. Following 1 h incubation with211At-rituximab, in concentrations which gave an initial activity of 50 kBq ml–1, a high tumour cell to normal bone marrow cell toxicity ratio was obtained; 4.1 to 1.0 log cell kill. Biodistribution studies of211At-rituximab in Balb/c mice showed similar stability as that of the iodinated analogue. The data indicate that testing of211At-rituximab in human patients is warranted. © 2000 Cancer Research Campaign
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References
Armitage JO (1993) Treatment of non-Hodgkin's lymphoma. N Engl J Med 328: 1023–1030
Barendsen GW, Koot CJ, Van Kersen GR, Bewley DK, Field SB and Parnell CJ (1965) The effect of oxygen on impairment of the proliferative capacity of human cells in culture by ionizing radiations of different LET. Int J Radiat Oncol Biol Phys 10: 317–327
Behr TM, Behe M, Stabin MG, Wehrmann E, Apostolidis C, Molinet R, Strutz F, Fayyazi A, Wieland E, Gratz S, Koch L, Goldenberg DM and 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
Brown I (1986) Astatine-211: its possible applications in cancer therapy. Int J Radiat Appl Instrum A 37: 789–798
Bruland OS (1995) Cancer therapy with radiolabelled antibodies. An overview. Acta Oncol 34: 1085–1094
Courtenay VD and Mills J (1978) An in vitro colony assay for human tumours grown in immune-suppressed mice and treated in vivo with cytotoxic agents. Br J Cancer 37: 261–268
Dyer MJ, Fischer P, Nacheva E, Labastide W and Karpas A (1990) A new human B-cell non-Hodgkin's lymphoma cell line (Karpas 422) exhibiting both t(14;18) and t(4;11) chromosomal translocations. Blood 75: 709–714
Eaves CJ, Cashman JD and Eaves AC (1991) Methodology of long-term culture of human hemopioetic cells. J Tiss Cult Meth 13: 55–62
Hall EJ (1994) Linear energy transfer and relative biological effectiveness. Radiobiology for the Radiologist, 153–164, Philadelphia, JB Lippincott Company
Harrison A and Royle L (1987) Efficacy of astatine-211-labeled monoclonal antibody in treatment of murine T-cell lymphoma. National Cancer Institute Monogr, 157–158
Kaminski MS, Zasadny KR, Francis IR, Fenner MC, Ross CW, Milik AW, Estes J, Tuck M, Regan D, Fisher S, Glenn SD and Wahl RL (1996) Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 14: 1974–1981
Knox SJ, Goris ML, Trisler K, Negrin R, Davis T, Liles TM, Grillo LA, Chinn P, Varns C, Ning SC, Fowler S, Deb N, Becker M, Marquez C and Levy R (1996) Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin Cancer Res 2: 457–470
Kvalheim G, Fodstad O, Pihl A, Nustad K, Pharo A, Ugelstad J and Funderud S (1987) Elimination of B-lymphoma cells from human bone marrow: model experiments using monodisperse magnetic particles coated with primary monoclonal antibodies. Cancer Res 47: 846–851
Larsen RH, Bruland OS, Hoff P, Alstad J, Lindmo T and Rofstad EK (1994a) Inactivation of human osteosarcoma cells in vitro by 211 At-TP-3 monoclonal antibody: comparison with astatine-211-labeled bovine serum albumin, free astatine-211 and external-beam X rays. Radiat Res 139: 178–184
Larsen RH, Hoff P, Alstad J and Bruland OS (1994b) Preparation and quality control of211At-labelled and125I-labelled monoclonal antibodies. Biodistribution in mice carrying human osteosarcoma xenografts. Journal of Labelled Compounds and Radiopharmaceuticals XXXIV: 774–785
Larsen RH, Slade S and Zalutsky MR (1998) Blocking [211At]astatide accumulation in normal tissues: preliminary evaluation of seven potential compounds. Nucl Med Biol 25: 351–357
Larsen RH, Murud KM, Akabani G, Hoff P, Bruland ØS and Zalutsky MR (1999) 211At- and131I-labelled bisphosphonates with high in vivo stability and bone accumulation. J Nucl Med 40: 1197–1203
Lindmo T, Boven E, Cuttitta F, Fedorko J and Bunn PA Jr (1984) Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 72: 77–89
Liu SY, Eary JF, Petersdorf SH, Martin PJ, Maloney DG, Appelbaum FR, Matthews DC, Bush SA, Durack LD, Fisher DR, Gooley TA, Bernstein ID and Press OW (1998) Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue. J Clin Oncol 16: 3270–3278
McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Brukler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D and Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16: 2825–2833
Multani PS and Grossbard ML (1998) Monoclonal antibody-based therapies for hematologic malignancies. J Clin Oncol 16: 3691–3710
Multani PS and Grossbard ML (1999) Antibody-based therapy for lymphoma. Adv Oncol 15: 23–29
Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S, Fisher DR, Porter B, Matthews DC and Gooley T (1995) Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet 346: 336–340
Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N and Anderson DR ( (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83: 435–445
Sgouros G, Ballangrud AM, Jurcic JG, McDevitt MR, Humm JL, Erdi YE, Mehta BM, Finn RD, Larson SM and Scheinberg DA (1999) Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia. J Nucl Med 40: 1935–1946
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Aurlien, E., Larsen, R., Kvalheim, G. et al. Demonstration of highly specific toxicity of the α-emitting radioimmunoconjugate 211At-rituximab against non-Hodgkin's lymphoma cells. Br J Cancer 83, 1375–1379 (2000). https://doi.org/10.1054/bjoc.2000.1453
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DOI: https://doi.org/10.1054/bjoc.2000.1453
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