Advertisement
Original paper| Volume 41, ISSUE 2, P151-161, November 1996

Download started.

Ok

Proposal for translational analysis and development of clinical radiolabeled immunoglobulin therapy

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Background and purpose: Radiolabeled immunoglobulin therapy (RIT) can be a selective, effective, low-toxicity outpatient cancer therapy. A consensus on the best approach for the preclinical and clinical development of RIT reagents needs to be developed. We report the M.D. Anderson Cancer Center prior experience in translating RIT from laboratory to clinic for the treatment of Hodgkin's disease and propose a flow diagram for the development of RIT for other malignancies.
      Material and methods: Three different animal models are described: nude mice bearing human tumor xenografts, normal beagle dogs, and normal rhesus monkeys. We produced and purified antibodies and prepared chelate-immunoconjugates reactive with six different human tumor-associated antigens. The Igs used were derived from rabbits, mice, and humans (human-derived RIT reagents being less immunogenic in human patients). Eighty patients with refractory Hodgkin's disease were treated with radiolabeled antiferritin.
      Results: We recommend a two-injection scheme using, (1) an indium-111-labeled radioimmunoconjugate for diagnosis, pharmacokinetic studies, and dosimetry, and (2) a yttrium-90-labeled radioimmunoconjugate for therapy. The animal models provide useful data on tumor targeting, radiotoxicology, and undesirable biodistributions. A 70% response rate is obtained in patients with advanced recurrent Hodgkin's disease. More extensive preclinical testing allows for safer and more effective clinical RIT studies.
      Conclusions: We recommend, (1) preclinical optimization of chelation chemistry, Ig size, Ig origin, route of administration, and fractionation, (2) new clinical Phase I–III studies more appropriate for RIT development than the classical Phase I–III studies used for the development of chemotherapeutic agents, and (3) more extensive preclinical testing of RIT reagents.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Radiotherapy and Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bierman P.J.
        • Vose J.M.
        • Leichner P.K.
        • Quadri S.M.
        • Armitage J.O.
        • Klein J.L.
        • Abrams R.A.
        • Dicke K.A.
        • Vriesendorp H.M.
        Yttrium-90-labeled antiferritin followed by high-dose chemotherapy and autologous bone marrow transplantation for poor prognosis Hodgkin's disease.
        J. Clin. Oncol. 1993; 11: 698-703
        • Buchsbaum D.J.
        • Khazaeli M.B.
        • Bright S.J.
        • Meredith R.F.
        Fractionated radioimmunotherapy of human colon carcinoma xenografts with 131-I-CC49 monoclonal antibody.
        J. Immunother. 1994; 16: 156
        • Chen P.F.
        • Freedman R.S.
        • Chernajarsky Y.
        • Platsoucas C.D.
        Amplification of immunoglobulin transcripts by the non-palindromic adoption polymerase chain reactive (NPA-PCR) nucleotide sequence analysis of two human monoclonal antibodies recognizing two cell surface antigens expressed in ovarian, cervix, breast, colon, and other carcinomas.
        Hum. Antibodies Hybridomas. 1994; 5: 131-143
        • Epenetos A.A.
        • Murro A.J.
        • Stewart S.
        • et al.
        Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies.
        J. Clin. Oncol. 1987; 5: 1890-1899
        • Fowler J.F.
        Radiobiological aspects of low dose rates in immunotherapy.
        Int. J. Radiat. Oncol. Biol. Phys. 1990; 18: 1261-1269
        • Freedman R.S.
        • Ioannides L.G.
        • Tomasonic B.
        • Patenia R.
        • Zhang H.Z.
        • Liang T.
        • Edwards C.L.
        Development of a cell surface-reacting human monoclonal antibody agent in ovarian carcinoma.
        Hybridoma. 1991; 10: 21-33
        • Goldenberg D.M.
        Future role of monoclonal antibodies in oncological diagnosis and therapy.
        in: Semin. Nucl. Med.19. 1989: 332-345
        • Grossbard M.L.
        • Press O.P.
        • Appelbaum F.R.
        • Bernstein I.D.
        • Nadler L.M.
        Monoclonal antibody-based therapies of leukemia and lymphoma.
        Blood. 1992; 80: 863-878
        • Herbst J.M.
        • Klein J.L.
        • Leichner P.K.
        • Quadri S.M.
        • Vriesendorp H.M.
        Survival of patients with resistant Hodgkin's disease after polyclonal yttrium-90-labeled antiferritin treatment.
        J. Clin. Oncol. 1995; 13: 2394-2400
        • Ingold J.H.
        • Reed G.B.
        • Kaplan H.S.
        • Bayshaw M.A.
        Radiation hepatitis.
        Am. J. Radiol. 1965; 93: 200-206
      1. Jaeckle, K. A. Paraneoplastic neurological diseases in cancer of the nervous system. Editor: V. Levin. Churchill Livingstone, New York (in press).

        • Lamki L.M.
        • Patt Y.Z.
        • Rosenblum M.G.
        • et al.
        Metastatic colorectal cancer: radioimmunoscintigraphy with a stabilized In-111-labeled F(ab′)2 fragment of an anti CEA monoclonal antibody.
        Radiology. 1990; 174: 147-151
        • Larson S.M.
        Lymphoma, melanoma, colon cancer diagnosis and treatment with radiolabeled monoclonal antibodies.
        Radiology. 1987; 165: 297-304
        • Leichner P.K.
        • Kwok C.S.
        Tumor dosimetry in radioimmunotherapy: methods of calculation for beta particles.
        Med. Phys. 1993; 29: 529-534
        • Leichner P.K.
        • Koral K.F.
        • Jaszczak R.J.
        • Green A.J.
        • Chen G.T.Y.
        • Roeske J.C.
        An overview of imaging techniques and physical aspects of treatment planning in radioimmunotherapy.
        Med. Phys. 1993; 20: 569-577
        • Lenhard R.E.
        • Order S.E.
        • Spunberg J.J.
        • Asbell S.O.
        • Leibel S.A.
        Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin's disease.
        J. Clin. Oncol. 1985; 3: 1296-1300
        • Markoe A.M.
        • Brady W.
        • Woo D.
        • et al.
        Treatment of gastrointestinal cancer using monoclonal antibodies.
        Front. Radiat. Ther. Oncol. 1990; 24: 214-224
        • Molthoff C.F.M.
        • Pinedo H.M.
        • Schlüper H.M.M.
        • Boven E.
        Influence of dose and schedule on the therapeutic efficacy of 131-I-labeled monoclonal antibody 139H2 in a human ovarian cancer xenograft model.
        Int. J. Cancer. 1992; 50: 474-480
        • Murray J.L.
        • Macey D.J.
        • Kasi L.P.
        • Rieger P.
        • et al.
        Phase II radioimmunotherapy trial with 131-I-CC49 in colorectal cancer.
        Cancer. 1994; 73: 1057-1066
        • Olive D.
        • Mawas C.
        Therapeutic applications of anti-CD4 antibodies.
        Crit. Rev. Ther. Drag Carrier Syst. 1993; 10: 29-63
        • Press D.W.
        • Eary J.F.
        • Badger C.C.
        High dose radioimmunotherapy of B cell lymphoma.
        Front. Radiat. Ther. Oncol. 1990; 24: 104-113
        • Quadri S.M.
        • Vriesendorp H.M.
        • Leichner P.R.
        • Williams J.R.
        Evaluation of indium-111 and yttrium-90 labeled linker-immunoconjugates in nude mice and dogs.
        J. Nucl. Med. 1993; 34: 938-945
        • Quadri S.M.
        • Mohammedpour H.
        A convenient synthesis of 2-p-aminobenzyl-3-methyl and 2-p-aminobenzyl-3-benzyl derivatives of diethylenetriaminepentaacetic acid (DTPA): carbon backbone-modified bifunctional chelating agents.
        Bioorg. Med. Chem. Lett. 1992; 2: 1661-1664
        • Quadri S.M.
        • Lai J.
        • Mohammadpour H.
        • Vriesendorp H.M.
        • Williams J.R.
        Assessment of radiolabeled stabilized F(ab′)2 fragments of monoclonal antiferritin antibody in a nude mouse model.
        J. Nucl. Med. 1993; 34: 2152-2159
        • Quadri S.M.
        • Siddigui A.
        • Klein J.L.
        • Vriesendorp H.M.
        Biodistribution and tumor localization of indium-111-labeled unmodified and modified F(ab′)2 fragments of human monoclonal IgM (16.88) in a nude mouse model.
        Nucl. Med. Biol. 1995; 22: 413-423
        • Quadri S.M.
        • Shao Y.
        • Blum J.E.
        • Leichner P.K.
        • Williams J.R.
        • Vriesendorp H.M.
        Preclinical evaluation of intravenously administered indium-111 and yttrium-90 labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs.
        Nucl. Med. Biol. 1993; 10: 559-570
        • Quadri S.M.
        • Malik A.B.
        • Tang X.Z.
        • Patenia R.
        • Freedman R.S.
        • Vriesendorp H.M.
        Preclinical analysis of intraperitoneal administration of indium-111-labeled human monoclonal IgM (AC6C3).
        Cancer Res. 1995; 55: 5736s-5742s
        • Riva R.
        • Arista A.
        • Tison V
        • Sturiale C.
        • et al.
        Intralesional radioimmunotherapy of malignant gliomas: an effective treatment in recurrent tumors.
        Cancer. 1994; 73: 1076-1082
        • Scheinberg D.A.
        • Lovett D.
        • Divgi C.R.
        • Graham M.C.
        • Berman E.
        • Pentlow K.
        • Feist N.
        • Finn R.D.
        • Clarkson B.D.
        • Gee T.S.
        • Larson S.M.
        • Oettgewn H.
        • Old L.J.
        A Phase I trial of monoclonal antibody M195 in acute myelogeneous leukemia: specific bone marrow targeting and internalization of radionuclides.
        J. Clin. Oncol. 1991; 24: 194-201
        • Schlom J.
        Monoclonal antibodies. They are more and less than you think.
        in: Broder S. Molecular Foundations of Oncology. Williams & Wilkins, Baltimore1991: 95-134
        • Schlom J.
        • Molinolio H.
        • Simpson J.F.
        • Siler K.
        • Roselli M.
        • Hinkle G.
        • Houchens D.P.
        • Colcher D.
        Advantage of dose fractionation in monoclonal antibody targeted radioimmunotherapy.
        J. Natl. Cancer Inst. 1990; 82: 763-771
        • Stewart F.A.
        Radiation nephropathy after abdominal irradiation or total body irradiation.
        Radiat. Res. 1995; 143: 235-237
        • Vaughan A.T.M.
        • Bradwell A.R.
        • Dykes P.W.
        • Anderson P.
        Illusions of tumor killing using radiolabeled antibodies.
        Lancet. 1986; 1: 1492-1493
        • Vriesendorp H.M.
        • Quadri S.M.
        • Stinson R.L.
        • Onyekwere O.C.
        • Shao Y.
        • Klein J.L.
        • Leichner P.K.
        • Williams J.R.
        Selection of reagents for human radioimmunotherapy.
        Int. J. Radiat. Oncol. Biol. Phys. 1992; 22: 37-45
        • Vriesendorp H.M.
        • Morton J.D.
        • Quadri S.M.
        A review of five consecutive studies of radiolabeled immunoglobulin therapy in patients with endstage Hodgkin's disease.
        Cancer Res. 1995; 55: 5888s-5892s
        • Vriesendorp H.M.
        • Quadri S.M.
        • Williams J.R.
        Radioimmunoglobulin therapy.
        in: Armitage J.O. Antman K.H. High Dose Cancer Therapy. Pharmacology, Hematopoietins, Stem Cells. Williams & Williams, Baltimore1992: 84-123 (Chapter 5)
        • Vriesendorp H.M.
        • Shao I.
        • Blum J.E.
        • Quadri S.M.
        • Williams J.R.
        Fractionated intravenous administration of site-specific yttrium-90 labeled B72.3 GYK DTPA immunoconjugate in beagle dogs.
        Nucl. Med. Biol. 1993; 20: 571-578
        • Vriesendorp H.M.
        • Herpst J.M.
        • Germack M.A.
        • Klein J.L.
        • Leichner P.K.
        • Loudenslager D.M.
        • Order S.E.
        Phase I-II studies of yttrium-labeled antiferritin for end-stage Hodgkin's disease including RTOG 87-01.
        J. Clin. Oncol. 1991; 9: 918-928
        • Vriesendorp H.M.
        Similarities between HL-A and major histocompatibility complexes of subhuman primates.
        in: Foglieni C.Scotti Pedroni G. Donati G.S. Cortesini R. Cortinovis R. Progressi nei Trapiante d'Organo e Negli Organi Artificiali. La Typografica Varese, 1976
        • Vriesendorp H.M.
        • Dicke K.A.
        • Quadri S.M.
        Radioimmunotherapy for bone marrow transplantation patients.
        in: Dicke K.A. Keating A. Proceedings of the 6th International Symposium on Autologus Bone Marrow Transplantation. Cancer Treatment Research Education Fund, Arlington, Texas1993: 98-101
        • Waldman H.
        Manipulation of T-cell responses with monoclonal antibodies.
        Annu. Rev. Immunol. 1989; 7: 407-444
        • Wang S.
        • Quadri S.M.
        • Tang X.Z.
        • Stephens L.C.
        • Lollo C.P.
        • Bartholomew R.M.
        • Vriesendorp H.M.
        Liver toxicity induced by combined external beam irradiation and radioimmunoglobulin therapy.
        Radiat. Res. 1995; 141: 294-302
        • Wilbur O.S.
        Potential use of alpha emitting radionuclides in the treatment of cancer.
        Antibody Immunoconjug. Radiopharm. 1991; 4: 85-97