Skip to main content
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1989 Mar;28(3):225–232. doi: 10.1007/BF00204993

Anti-idiotypic monoclonal antibody to a T-cell chronic lymphatic leukemia

Characterization of the antibody, in vitro effector functions and results of therapy

Carl Harald Janson 1,, Mahmood Jeddi Tehrani 1, H»kan Mellstedt 3, Hans Wigzell 1
PMCID: PMC11041056  PMID: 2784357

Abstract

A murine anti-idiotypic monoclonal antibody (mAb), F1, (IgG2a) was produced against the variable part of the T-cell receptor for antigen (Ti, α/β) on the tumor cells of a patient with T-cell chronic lymphatic leukemia (CD3+, 8+, 4). The molecular weight of the protein reactive with mAb F1, comodulation and coprecipitation with anti-CD3 antibody, and the restricted tumor-cell reactivity strongly support the anti-idiotypic nature of mAb F1. MAb F1 also stained ≤4% of peripheral blood lymphocytes of healthy donors. MAb F1 did not stimulate the tumor cells to DNA synthesis, but stimulated a fraction of the normal peripheral blood lymphocytes, mAb F1 did not mediate antibody-dependent cellular cytotoxicity or complement lysis to any significant degree in vitro. Three infusions of 1–10 mg anti-idiotypic mAb were given over a period of 4 weeks. The plasma half-life for mAb F1 was 3 h in the first 2 h after infusion and 44 h from 2 h to 120 h after infusion. After each treatment a rapid decrease of circulating tumor cells was seen. During the observation period an 80% reduction of the total circulating tumor cells was noted. After the second infusion, IgM and IgG antimouse antibodies were detected. Side-effects from therapy were fever, chills, nausea, vomiting, diarrhea, tachycardia, increase in systolic blood pressure and shortness of breath. Thus, in T-cell malignancies a major reduction of circulating tumor cells can be accomplished by low doses of anti-idiotypic mAb. Anti-idiotypic mAb might be a therapeutic agent of significant importance.

Keywords: Peripheral Blood Lymphocyte, Circulate Tumor Cell, Variable Part, Cellular Cytotoxicity, Major Reduction

References

  • 1.Acuto O, Hussey RE, Fitzgerald KA, Protentis JP, Meuer SC, Schlossman SF, Reinherz EL. The human T-cell receptor: appearance in ontogeny and biokemical relationship of α and β subunits on IL-2 dependent clones and T-cell tumors. Cell. 1983;34:717. doi: 10.1016/0092-8674(83)90528-7. [DOI] [PubMed] [Google Scholar]
  • 2.Anasetti C, Martin PJ, Morishita Y, Badger CC, Bernstein ID, Hansen JA. Human large granular lymphocytes express high affinity receptors for murine monoclonal antibodies of the IgG3 subclass. J Immunol. 1987;138:2979. [PubMed] [Google Scholar]
  • 3.Ashwell JD, Longo DL, Bridges SH. T-cell tumor elimination as a result of T-cell receptor-mediated activation. Science. 1987;237:61. doi: 10.1126/science.3037698. [DOI] [PubMed] [Google Scholar]
  • 4.Bertram JH, Gill PS, Levine AM, Boquiren D, Hoffman FM, Meyer P, Mitchell MS. Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic and immunologic correlation. Blood. 1986;68:752. [PubMed] [Google Scholar]
  • 5.Bridges CDB. A method for preparing stable digitonin solutions for visual pigment extractions. Vision Res. 1977;17:301. doi: 10.1016/0042-6989(77)90095-5. [DOI] [PubMed] [Google Scholar]
  • 6.Capel PJA, Preijers FWMB, Allebes WA, Haanen C. Treatment of chronic lymphocytic leukaemia with monoclonal anti-idiotypic antibody. Neth J Med. 1985;28:112. [PubMed] [Google Scholar]
  • 7.Denkers EY, Badger CC, Ladbetter JA, Bernstein ID. Influence of antibody isotype on passive serotherapy of lymphoma. J Immunol. 1985;135:2183. [PubMed] [Google Scholar]
  • 8.Dillman RO, Shawler DL, Sobol RE, Collins HA, Beauregard JC, Wormsley SB, Royston I. Murine monoclonal antibody therapy in two patients with chronic lymphocytic leukemia. Blood. 1982;59:1036. [PubMed] [Google Scholar]
  • 9.Dillman RO, Beauregard J, Shawler DL, Halpern SE, Markman M, Ryan KP, Baird SM, Clutter M. Continuous infusion of T101 monoclonal antibody in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. J Biol Response Mod. 1986;5:394. [PubMed] [Google Scholar]
  • 10.Douillard JY, Lehur PA, Vignoud J, Blottière H, Maurel C, Thedrey P, Kremer M, LeMevel B. Monoclonal antibodies specific immunotherapy of gastrointestinal tumors. Hybridoma. 1986;5:139. [PubMed] [Google Scholar]
  • 11.Foon KA, Schroff RW, Bunn PA, Mayer D, Abrams PG, Fer M, Ochs J, Bottino GC, Sherwin SA, Carlo DJ, Heberman RB, Oldham RK. Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia. Blood. 1984;64:1085. [PubMed] [Google Scholar]
  • 12.Frödin J-E, Biberfeld P, Christenssen B, Philstedt P, Semdelius S, Sylvén M, Wahren B, Koprowski H, Mellstedt H. Treatment of patients with metastasizing colorectal carcinoma with mouse monoclonal antibodies (Moab 17-1A): a progress report. Hybridoma. 1986;5:151. [PubMed] [Google Scholar]
  • 13.Hamblin TJ, Abdul-Ahad AK, Gordon J, Stevenson FK, Stevenson GT. Preliminary experience in treating lymphocytic leukemia with antibody to immunoglobulin idiotypes on the cell surfaces. Br J Cancer. 1980;42:495. doi: 10.1038/bjc.1980.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Hamblin TJ, Cattan AR, Glennie MJ, MacKenzie MR, Stevenson FK, Watts HF, Stefenson GT. Initial experience in treating human lymphoma with a chimeric univalent derivative of monoclonal anti-idiotypic antibody. Blood. 1987;69:790. [PubMed] [Google Scholar]
  • 15.Herlyn D, Koprowski H. IgG2a monoclonal antibodies inhibit human tumor growth through interaction with effector cells. Proc Natl Acad Sci USA. 1985;79:4761. doi: 10.1073/pnas.79.15.4761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed MR, Oettgen HF, Old LJ. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl Acad Sci USA. 1985;82:1242. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Janson CH, Tehrani M, Mellstedt H, Wigzell H. Three kinds of tumor-unique surface molecules on a human T-cell chronic lymphocytic leukaemia (T-CLL) detected by monoclonal antibodies. Scand J Immunol. 1987;26:237. doi: 10.1111/j.1365-3083.1987.tb02257.x. [DOI] [PubMed] [Google Scholar]
  • 18.Kaminski MS, Kitamura K, Maloney DG, Campbell MJ, Levy R. Importance of antibody isotype in monoclonal anti-idiotypic therapy of a murine B cell lymphoma. A study of hybridoma class switch variants. J Immunol. 1986;136:1123. [PubMed] [Google Scholar]
  • 19.Kipps TJ, Parham P, Punt J, Herzenberg LA. Importance of immunoglobulin isotype in human antibody-dependent, cell-mediated cytotoxicity directed by murine monoclonal antibodies. J Exp Med. 1985;161:1. doi: 10.1084/jem.161.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Köhler G. Hybridoma techniques, EMBO, SKMB Course. Basel: Basel Institute for Immunology; 1980. [Google Scholar]
  • 21.Köhler G, Millstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  • 22.Kubagawa H, Mayumi M, Gathings WD, Karney JF, Cooper MD. Advances in cell biology and treatment. Amsterdam: Elsevier; 1983. Extent of clonal involvement in B cell malignancies; p. 65. [Google Scholar]
  • 23.Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  • 24.Landegren U. Measurement of cell number using an endogenous enzyme, hexosaminidase. Applications for the detection of lymphokines and cell surface antigens. J Immunol Methods. 1984;67:379. doi: 10.1016/0022-1759(84)90477-0. [DOI] [PubMed] [Google Scholar]
  • 25.Levy R, Levy S, Cleary ML, Carroll W, Kon S, Bird J, Sklar J. Somatic mutation in human B-cell tumors. Immunol Rev. 1987;96:43. doi: 10.1111/j.1600-065x.1987.tb00508.x. [DOI] [PubMed] [Google Scholar]
  • 26.Lowder JN, Meeker TC, Campbell M, Garcia CF, Gralow J, Miller RA, Warnke R, Levy R. Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: Correlation with clinical response. Blood. 1987;69:199. [PubMed] [Google Scholar]
  • 27.Meeker T, Lowder J, Cleary ML, Stewart S, Warnke R, Sklar J, Levy R. Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies. N Engl J Med. 1985;312:1658. doi: 10.1056/NEJM198506273122602. [DOI] [PubMed] [Google Scholar]
  • 28.Meeker TC, Lowder JN, Maloney DG, Miller RA, Thielemanns K, Warnke R, Levy R. A clinical trial of antiidiotype therapy for B cell malignancy. Blood. 1985;65:1349. [PubMed] [Google Scholar]
  • 29.Mellstedt H, Frödin JE, Christiensson B, Shetye J, Biberfeld P, Lefvert AK, Pihlstedt P, Sylvén M, Mahower J, Wahren B, Ahlman B, Cedemark B, Erwald R, Klingenström P, Nathansson J, Rieger Å, Koprowski H. Monoclonal antibodies in oncology. New York: Marcel Dekker Inc; 1988. Application of monoclonal antibodies (mAb 17-1A) in the treatment of colorectal carcinomas. [Google Scholar]
  • 30.Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL. Clonotypic structures involved in antigen-specific human T cell function. J Exp Med. 1983;157:705. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982;306:517. doi: 10.1056/NEJM198203043060906. [DOI] [PubMed] [Google Scholar]
  • 32.Miller RA, Oseroff AR, Stratte PT, Levy R. Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma. Blood. 1983;62:988. [PubMed] [Google Scholar]
  • 33.Miller RA, Lowder JN, Gralow J, Meeker T, Levy R. In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias. Blood. 1987;69:1249. [PubMed] [Google Scholar]
  • 34.Nadler LM, Stashenko P, Hard R, Kaplan WD, Button LN, Kufe DW, Antman KH, Schlossman SF. Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res. 1980;40:3147. [PubMed] [Google Scholar]
  • 35.Oettgen HC, Kappler J, Tax WJM, Terhorst C. Characterization of the two heavy chains of the T3 complex on the surface of human T lymphocytes. J Biol Chem. 1984;259:12039. [PubMed] [Google Scholar]
  • 36.Oettgen HC, Pettey CL, Maloy WL, Terhorst C. A T3-like protein complex associated with the antigen receptor on murine T cells. Nature. 1986;320:272. doi: 10.1038/320272a0. [DOI] [PubMed] [Google Scholar]
  • 37.Oldham RK, Foon KA, Morgan AC, Woodhouse CS, Schroff RW, Abrams PG, Fer M, Schoenbergen CS, Farrel M, Kimball E, Sheriv SA. Monoclonal antibody therapy of malignant melanomas: in vitro localization in cutaneous metastasis after intravenous administration. J Clin Oncol. 1984;2:1235. doi: 10.1200/JCO.1984.2.11.1235. [DOI] [PubMed] [Google Scholar]
  • 38.Ortaldo JR, Woodhouse C, Morgan AC, Herberman RB, Cheresh DA, Reisfeld P. Analysis of effector cells in human antibody-dependent cellular cytotoxicity with murine monoclonal antibodies. J Immunol. 1987;138:3566. [PubMed] [Google Scholar]
  • 39.Ponticelli C, Rivolta E, Tarantino A, Egidi F, Banfi G, DeVecchi A, Montagnino G, Vegeto A. Clinical experience with orthoclone OKT3 in renal transplantation. Transplantation Proceedings. 1986;4:942. [Google Scholar]
  • 40.Press OW, Appelbaum F, Ledbetter JA, Martin PJ, Zarling J, Kidd P, Thomas ED. Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B CLL lymphomas. Blood. 1987;69:584. [PubMed] [Google Scholar]
  • 41.Rankin EM, Hekman A, Somers R, ten Bokkel Huinink W. Treatment of two patients with B cell lymphoma with monoclonal anti-idiotype antibodies. Blood. 1985;65:1373. [PubMed] [Google Scholar]
  • 42.Ritz J, Pesando JM, Sallen SE, Clavell LA, Notis-McConarty J, Rosenthal P, Schlossman SF. Serotherapy of acute lymphoblastic leukemia with monoclonal antibody. Blood. 1981;58:141. [PubMed] [Google Scholar]
  • 43.Schroff RW, Farrell MM, Klein RA, Oldham RK, Foon KA. T65 antigen modulation in a phase 1 monoclonal antibody trial with chronic lymphocytic leukemia patients. J Immunol. 1984;133:1641. [PubMed] [Google Scholar]
  • 44.Verrill H, Goldberg M, Rosenbaum R, Abbot R, Simunovic L, Steplewski Z, Koprowski H. Clinical trial of Unistar Institute 17-1A monoclonal antibody in patients with advanced gastrointestinal adenocarcinoma: a preliminary report. Hybridoma. 1986;5:175. [PubMed] [Google Scholar]
  • 45.Weiss A, Newton M, Crommie D. Expression of T3 in association with a molecule distinct from the T-cell antigen receptor heterodimer. Proc Natl Acad Sci USA. 1986;83:6998. doi: 10.1073/pnas.83.18.6998. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES