Abstract
Repeated therapy of cancer with mouse monoclonal antibodies frequently produces antibodies directed against the administered antibody. We have investigated the ability of cyclosporin A (CsA) and the use of ultracentrifuged antibody to prevent the formation of anti-antibodies in rabbits. Courses of CsA, 20 mgkg-1 day-1, were given intramuscularly for 6 days to rabbits and a mouse monoclonal anti-human chorionic gonadotrophin antibody was given intravenously on day 2 with or without ultracentrifugation to remove microaggregates. The whole course was repeated after an interval of two weeks. Rabbit anti-mouse antibody production was prevented in all 8 animals that were given CsA and ultracentrifuged preparation (non UC-W14). Anti-mouse antibody was produced by all the animals that were not given CsA. A further dose of mouse antibody eight weeks after CsA demonstrated that immunological recovery had occurred in all four animals re-challenged with non UC-W14 but only 3/7 animals given an UC-W14 preparation. This suggests that CsA and ultracentrifugation facilitate the induction of immunological tolerance. The complete suppression of antibody production which could be achieved justifies a clinical trial of CsA and ultracentrifugation of antibody.
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Selected References
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- Ada G. L., Byrt P. Specific inactivation of antigen-reactive cells with 125I-labelled antigen. Nature. 1969 Jun 28;222(5200):1291–1292. doi: 10.1038/2221291a0. [DOI] [PubMed] [Google Scholar]
- BIRO C. E., GARCIA G. THE ANTIGENICITY OF AGGREGATED AND AGGREGATE-FREE HUMAN GAMMA-GLOBULIN FOR RABBITS. Immunology. 1965 Apr;8:411–419. [PMC free article] [PubMed] [Google Scholar]
- Benjamin R. J., Cobbold S. P., Clark M. R., Waldmann H. Tolerance to rat monoclonal antibodies. Implications for serotherapy. J Exp Med. 1986 Jun 1;163(6):1539–1552. doi: 10.1084/jem.163.6.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Borel J. F., Feurer C., Gubler H. U., Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions. 1976 Jul;6(4):468–475. doi: 10.1007/BF01973261. [DOI] [PubMed] [Google Scholar]
- Borel J. F., Feurer C., Magnée C., Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017–1025. [PMC free article] [PubMed] [Google Scholar]
- Carrasquillo J. A., Krohn K. A., Beaumier P., McGuffin R. W., Brown J. P., Hellström K. E., Hellström I., Larson S. M. Diagnosis of and therapy for solid tumors with radiolabeled antibodies and immune fragments. Cancer Treat Rep. 1984 Jan;68(1):317–328. [PubMed] [Google Scholar]
- DRESSER D. W., GOWLAND G. IMMUNOLOGICAL PARALYSIS INDUCED IN ADULT RABBITS BY SMALL AMOUNTS OF A PROTEIN ANTIGEN. Nature. 1964 Aug 15;203:733–736. doi: 10.1038/203733a0. [DOI] [PubMed] [Google Scholar]
- DRESSER D. W. Specific inhibition of antibody production. II. Paralysis induced in adult mice by small quantities of protein antigen. Immunology. 1962 May;5:378–388. [PMC free article] [PubMed] [Google Scholar]
- Green C. J., Allison A. C. Extensive prolongation of rabbit kidney allograft survival after short-term cyclosporin-A treatment. Lancet. 1978 Jun 3;1(8075):1182–1183. doi: 10.1016/s0140-6736(78)90970-4. [DOI] [PubMed] [Google Scholar]
- Hess A. D., Colombani P. M., Esa A. H. Cyclosporine and the immune response: basic aspects. Crit Rev Immunol. 1986;6(2):123–149. [PubMed] [Google Scholar]
- Jaffers G. J., Fuller T. C., Cosimi A. B., Russell P. S., Winn H. J., Colvin R. B. Monoclonal antibody therapy. Anti-idiotypic and non-anti-idiotypic antibodies to OKT3 arising despite intense immunosuppression. Transplantation. 1986 May;41(5):572–578. doi: 10.1097/00007890-198605000-00004. [DOI] [PubMed] [Google Scholar]
- Klaus G. G., Kunkl A. Effects of cyclosporine on the immune system of the mouse. II. Cyclosporine inhibits the effector function of primary T helper cells, but not helper cell priming. Transplantation. 1983 Jul;36(1):80–84. doi: 10.1097/00007890-198307000-00016. [DOI] [PubMed] [Google Scholar]
- Lindsey N. J., Harris K. R., Norman H. B., Smith J. L., Lee H. A., Slapek M. The effect of cyclosporin A on the primary and secondary immune responses in the rabbit. Transplant Proc. 1980 Jun;12(2):252–255. [PubMed] [Google Scholar]
- 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. 1985 Jun;65(6):1349–1363. [PubMed] [Google Scholar]
- Miller R. A., Oseroff A. R., Stratte P. T., Levy R. Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma. Blood. 1983 Nov;62(5):988–995. [PubMed] [Google Scholar]
- Riechmann L., Clark M., Waldmann H., Winter G. Reshaping human antibodies for therapy. Nature. 1988 Mar 24;332(6162):323–327. doi: 10.1038/332323a0. [DOI] [PubMed] [Google Scholar]
- Rossen R. D., Butler W. T., Nora J. J., Fernbach D. J. Preventing antibody formation to anti-lymphocytic globulin in man. J Immunol. 1971 Jan;106(1):11–19. [PubMed] [Google Scholar]
- Schroff R. W., Foon K. A., Beatty S. M., Oldham R. K., Morgan A. C., Jr Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy. Cancer Res. 1985 Feb;45(2):879–885. [PubMed] [Google Scholar]
- Searle F., Partridge C. S., Kardana A., Green A. J., Buckley R. G., Begent R. H., Rawlins G. A. Preparation and properties of mouse monoclonal antibody (W14A) to human chorionic gonadotropin. Int J Cancer. 1984 Apr 15;33(4):429–434. doi: 10.1002/ijc.2910330402. [DOI] [PubMed] [Google Scholar]
- Sears H. F., Atkinson B., Mattis J., Ernst C., Herlyn D., Steplewski Z., Häyry P., Koprowski H. Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours. Lancet. 1982 Apr 3;1(8275):762–765. doi: 10.1016/s0140-6736(82)91811-6. [DOI] [PubMed] [Google Scholar]
- Sears H. F., Herlyn D., Steplewski Z., Koprowski H. Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. J Biol Response Mod. 1984;3(2):138–150. [PubMed] [Google Scholar]
- Shawler D. L., Bartholomew R. M., Smith L. M., Dillman R. O. Human immune response to multiple injections of murine monoclonal IgG. J Immunol. 1985 Aug;135(2):1530–1535. [PubMed] [Google Scholar]
- Smith G. N. The effect of cyclosporin A on the primary immune response to allogeneic red cells in rabbits. Immunology. 1982 Jan;45(1):163–167. [PMC free article] [PubMed] [Google Scholar]
- Taub R. N., Kochwa S., Brown S. M., Rubin A. D., Dameshek W. Antigen-induced immunological tolerance in man to equine anti-human-thymocyte gamma-globulin. Lancet. 1969 Sep 6;2(7619):521–523. doi: 10.1016/s0140-6736(69)90219-0. [DOI] [PubMed] [Google Scholar]
- Thistlethwaite J. R., Jr, Cosimi A. B., Delmonico F. L., Rubin R. H., Talkoff-Rubin N., Nelson P. W., Fang L., Russell P. S. Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection. Transplantation. 1984 Dec;38(6):695–701. doi: 10.1097/00007890-198412000-00029. [DOI] [PubMed] [Google Scholar]
