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The clinical use of monoclonal antibodies, MAb 17-1A, in the treatment of patients with metastatic colorectal carcinoma

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Abstract

Increasing doses of MAb 17-1A (mouse IgG2A) have been given for therapy of patients with metastatic colorectal carcinoma (n = 28). Serum half-life (Tβ1/2l) of MAb 17-1A after a single infusion was about 24 h. A constant serum level of MAb 17-1A could be maintained for a long time period by infusions every 2–3 days. Patients received 500 mg 3 days a week for 12 weeks (total dose 12 g). Side effects were mild and dose related but never required medical intervention except for three times (out of 243 infusions) when allergic reactions appeared. All patients developed IgM and IgG antibodies. Two patients experienced immune complex-related symptoms. Six out of 22 evaluable patients (27%) had objective evidence of tumor cell regression/lysis. One of these achieved a complete remission. Median survival for all patients was 12 months, for responding patients 19 months and for non-responding 11 months. 5/17 patients were studied for the development of anti-anti-idiotyplc antibodies (Ab3). The presence of Ab3 in serum correlated favourably to the clinical outcome of the disease.

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References

  1. Herlyn D, Steplewski Z, Herlyn M, Koprowski H: Inhibition of growth of colorectal carcinoma in nude mice by monoclonal antibody.Cancer Res 40, 717 (1980).

    PubMed  CAS  Google Scholar 

  2. Adams D O, Hall T, Steplewski Z, Koprowski H: Tumors undergoing rejection induced by monoclonal antibodies of the IgG2A isotype contain increased numbers of macrophages activated for a distinctive form of antibody-dependent cytolysis.Proc natn Acad Sci USA 81, 3506 (1984).

    Article  CAS  Google Scholar 

  3. Schulz G, Staffileno L K, Reisfeld R A, Dennert G: Eradication of established human melanoma tumor in nude mice by antibody-directed effector cells.J exp Med 161, 1315 (1985).

    Article  PubMed  CAS  Google Scholar 

  4. Steplewski Z, Herlyn D, Lübeck M, Kimoto Y, Herlyn M, Koprowski H: Mechanisms of tumor growth inhibition.Hybridoma 5, 59 (1986).

    Google Scholar 

  5. Meeker T C, Lowder J, Maloney D G, Miller R A, Thielemans K, Warnke R, Levy R: A clinical trial of anti-idiotype therapy for B cell malignancy.Blood 65, 1349 (1985).

    PubMed  CAS  Google Scholar 

  6. Koprowski H, Herlyn D, Lubeck M, DeFreitas E, Sears H F: Human anti-idiotype antibodies in cancer patients: is the modulation of the immune response beneficial for the patient?Proc natn Acad Sci USA 81, 216 (1984).

    Article  CAS  Google Scholar 

  7. Koprowski H, Steplewski Z, Mitchall K, Herlyn M, Herlyn D, Fuhrer P: Colorectal carcinoma antigens detected by hybridoma antibodies.Somat Cell Genet 5, 957 (1979).

    Article  PubMed  CAS  Google Scholar 

  8. Ross A H, Lubeck M, Steplewski Z, Koprowski H: Identification and characterization of the CO17-1A carcinoma-associated antigen.Hybridoma 5, 21 (1986).

    Article  Google Scholar 

  9. Göttlinger H, Johnsson J, Mietmüller G: Biochemical and epitope analysis of the 17-1A membrane antigen.Hybridoma 5, 29 (1986).

    Google Scholar 

  10. Herlyn M, Steplewski Z, Herlyn D, Koprowski H: Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies.Proc natn Acad Sci USA 76, 1438 (1979).

    Article  CAS  Google Scholar 

  11. Shetye J, Frödin J-E, Christensson B, Grant C, Jacobsson B, Sundelius S, Sylvén M, Biberfeld P, Mellstedt H: Immunohistochemical monitoring of metastatic colorectal carcinoma in patients treated with monoclonal antibodies (MAb 17-1A).Cancer Immun Immunother, in press.

  12. Pimm M V, Baldwin R W: Localization of an antitumor monoclonal antibody in human tumor xenografts: kinetic and quantitative studies with the 791T/36 antibody, in Baldwin R W, Byers V S (eds):Monoclonal Antibodies for Cancer Detection and Therapy, p. 97. New York, Academic Press (1985).

    Google Scholar 

  13. Herlyn D, Powe J, Ross A K, Herlyn M, Koprowski H: Inhibition of human tumor growth by IgG2A monoclonal antibodies correlates with antibody density on tumor cells.J Immun 134, 1300 (1985).

    PubMed  CAS  Google Scholar 

  14. Steinitz M, Tamir S, Pizov G, Fröclin J-E, Lefvert A-K, Mellstedt H: Human monoclonal antiidiotyplc antibodies. I. Establishment of immortalized cell lines from a tumor patient treated with mouse monoclonal antibodies.J. Immun, in press.

  15. Herlyn D, Sears H, Iliopoulos D, Lubeck M, Douillard J-Y, Sindelar W, Tempero M, Mellstedt H, Maher M, Koprowski H: Anti-idiotyplc antibodies to monoclonal antibody CO17-1A.Hybridoma 5, 51 (1986).

    Google Scholar 

  16. Steplewski Z: Wistar Symposium on Immunodiagnosis and Immunotherapy with CO17-1A MAb in Gastrointestinal Cancer.Hybridoma 5 (Suppl. 1) (1986).

  17. Mellstedt H, Fröclin J-E, Christensson B, Shetye J, Biberfeld P, Lefvert A-K, Pihlstedt P, Sylvén M, Makower J, Wahren B, Ahlman B, Cedermark B, Erwald R, Klingenström P, Nathansson J, Rieger Å, Koprowski H: Application of monoclonal antibodies (MAb 17-1A) in the treatment of colorectal carcinomas, in Carrano R A, Douillard J Y (eds):Monoclonal Antibodies in Clinical Oncology. New York, Marcek Dekker, in press.

  18. Bergmark S, Hafström L O: The natural history of primary and secondary malignant tumors of the liver. I. The prognosis for patients with hepatic metastases from colonic and rectal carcinomas by laparotomy.Cancer 23, 198 (1969).

    Article  Google Scholar 

  19. Beckström A Y, Hafström L O: Prognostic factors influencing survival of patients with advanced colorectal cancer: hepatic-artery infusion versus systemic intravenous chemotherapy for liver metastases.J clin Oncol 2, 174 (1984).

    Google Scholar 

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Mellstedt, H., Frödin, J.E., Ragnhammar, P. et al. The clinical use of monoclonal antibodies, MAb 17-1A, in the treatment of patients with metastatic colorectal carcinoma. Med. Oncol. & Tumor Pharmacother. 6, 99–107 (1989). https://doi.org/10.1007/BF02985230

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