Abstract
Cyclosporin A (CsA) is an effective modulator of multidrug resistance (MDR) in vitro and in murine tumour systems in vivo. We now report the production of immunity to L1210 leukaemia by the addition of CsA to VP-16 therapy of leukaemic BDF/1 mice. VP-16/cyclosporin A tumour immunity induction arises as a consequence of active therapy independently of immunisation with modified tumour cells. The addition of CsA to VP-16 prolongs survival of BDF/1 host mice bearing L1210 leukaemia beyond that produced by equivalent dose VP-16 alone. A subpopulation of 60-day surviving mice after combined VP-16/CsA are immune to rechallenge with the same leukaemia inoculum to which they were originally exposed. Spleen cells from immune mice adoptively transfer anti-L1210 leukaemia immunity to untreated BDF/1 mice in a dose dependent, statistically significant manner. Adoptive transfer experiments additionally suggest active recruitment of immunologic response in recipient animals: (1) We have been able to perpetuate leukaemia immunity in four sequential cohorts of naive recipient mice. This propogation of adoptive immunity is accomplished by use of spleen cells harvested from each preceeding passively-protected animal cohort; (2) Cyclophosphamide pretreatment of adoptive transfer recipient mice abrogates the ability of their splenocytes to perpetuate passive protection in sequential adoptive transfer experiments.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barker E., Mokyr M. B. Importance of Lyt-2+ T-cells in the resistance of melphalan-cured MOPC-315 tumor bearers to a challenge with MOPC-315 tumor cells. Cancer Res. 1988 Sep 1;48(17):4834–4842. [PubMed] [Google Scholar]
- Berendt M. J., North R. J. T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med. 1980 Jan 1;151(1):69–80. doi: 10.1084/jem.151.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Canafax D. M., Ascher N. L. Cyclosporine immunosuppression. Clin Pharm. 1983 Nov-Dec;2(6):515–524. [PubMed] [Google Scholar]
- GOLDIN A., HUMPHREYS S. R. Studies of immunity in mice surviving systemic leukemia L1210. J Natl Cancer Inst. 1960 Feb;24:283–300. [PubMed] [Google Scholar]
- GOLDIN A., HUMPHREYS S. R., VENDITTI J. M., MANTEL N. Prolongation of the lifespan of mice with advanced leukemia (L1210) by treatment with halogenated derivatives of amethopterin. J Natl Cancer Inst. 1959 Apr;22(4):811–823. [PubMed] [Google Scholar]
- Geller R. B., Esa A. H., Beschorner W. E., Frondoza C. G., Santos G. W., Hess A. D. Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat. Blood. 1989 Aug 15;74(3):1165–1171. [PubMed] [Google Scholar]
- Glazier A., Tutschka P. J., Farmer E. R., Santos G. W. Graft-versus-host disease in cyclosporin A-treated rats after syngeneic and autologous bone marrow reconstitution. J Exp Med. 1983 Jul 1;158(1):1–8. doi: 10.1084/jem.158.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hess A. D., Horwitz L., Beschorner W. E., Santos G. W. Development of graft-vs.-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity. J Exp Med. 1985 Apr 1;161(4):718–730. doi: 10.1084/jem.161.4.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hess A. D., Tutschka P. J. Effect of cyclosporin A on human lymphocyte responses in vitro. I. CsA allows for the expression of alloantigen-activated suppressor cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR. J Immunol. 1980 Jun;124(6):2601–2608. [PubMed] [Google Scholar]
- Mihich E. Combined effects of chemotherapy and immunity against leukemia L1210 in DBA-2 mice. Cancer Res. 1969 Apr;29(4):848–854. [PubMed] [Google Scholar]
- Mokyr M. B., Dray S. Some advantages of curing mice bearing a large subcutaneous MOPC-315 tumor with a low dose rather than a high dose of cyclophosphamide. Cancer Res. 1983 Jul;43(7):3112–3119. [PubMed] [Google Scholar]
- Moore M., Williams D. E. Contribution of host immunity to cyclophosphamide therapy of a chemically-induced murine sarcoma. Int J Cancer. 1973 Mar 15;11(2):358–368. doi: 10.1002/ijc.2910110213. [DOI] [PubMed] [Google Scholar]
- North R. J. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med. 1982 Apr 1;155(4):1063–1074. doi: 10.1084/jem.155.4.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakaguchi S., Sakaguchi N. Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A-treated mice causes organ-specific autoimmune disease in athymic nude mice. J Exp Med. 1988 Apr 1;167(4):1479–1485. doi: 10.1084/jem.167.4.1479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skipper H. E. The effects of chemotherapy on the kinetics of leukemic cell behavior. Cancer Res. 1965 Oct;25(9):1544–1550. [PubMed] [Google Scholar]
- Slater L. M., Sweet P., Stupecky M., Gupta S. Cyclosporin A reverses vincristine and daunorubicin resistance in acute lymphatic leukemia in vitro. J Clin Invest. 1986 Apr;77(4):1405–1408. doi: 10.1172/JCI112450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slater L. M., Sweet P., Stupecky M., Wetzel M. W., Gupta S. Cyclosporin A corrects daunorubicin resistance in Ehrlich ascites carcinoma. Br J Cancer. 1986 Aug;54(2):235–238. doi: 10.1038/bjc.1986.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
