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Pharmacologic manipulation of tumor cell immunogenicity (xenogenization) as a means of inducing their rejection in experimental immunotherapy
318
Pharmaco~gmal Resea~h Commun~ation~ Vo~ 2~ Supp~ment ~ 1988
P H A R M A C O L O G I C M A N I P U L A T I O N OF TUMOR C E L L IMMUNOGENICITY
(XENOGENIZATION)
AS A MEANS OF INDUCING T H E I R REJECTION IN EXPERIMENTAL IMMUNOTHERAPY
P. Puccetti, R. Bianchi, L. Romani, M.C. Fioretti Pharmacology Section, Dept. Exp. Med., University of Perugia Key words: Xenogenization, Mutagens, Immunotherapy Chemically xenogenized murine lymphomas carry novel antigenic determinants (drug-mediated tumor antigens or DMTA) responsible for their own rejection in histocompatible hosts and for protection against the original, poorly immunogenic cells when used as a tumor cell vaccine. Lymphocytes immune to xenogenized tumors are protective when adoptively transferred to naive recipient mice challenged with the original cells. Therefore, co-expression of DMTA and naturally occurring tumor antigens
(TATA) makes the latter suit-
able targets for potent antitumor immune responses. In the present communication we comparatively analyze the immune mechanisms triggered by DMTA and TATA, respectively, in antitumor immunotherapy models. In particular, we show that otherwise poorly immunogenic TATA, when coupled with DMTA, evoke a cellular immune response with the features of a delayed-type hypersensitivity reaction. This reaction involves induction of specifically immune T lymphocytes with the "helper" surface antigen phenotype, release of gamma interferon, and activation of tumoricidal macrophages in the host. Therefore, DMTA play a crucial role as adjuvant determinants in the triggering of TATA-specific antitumor responses that can be successfully ex ~ ploited in experimental models of tumor immunotherapy. DMTA, on the other hand, also induce specific responses that are primarily mediated by cytotoxic T lymphocytes and can be likewise used in immunotherapy protocols of xenogenized tumors grafted in deliberately immunodepressed recipient hosts. REFERENCES:
Puccetti P., Romani L. and Fioretti MC.
(1987) Cancer Metast. Rev. 6:93-111
Bianchi R., Romani L., Puccetti P. and Fioretti MC.
(1987) Int. J.
Cancer 40:7-11 Work supported by CNR-Italy grant N. 87.02806.44 within Progetto Finalizzato Oncologia.
Pharmaco~gmal Resea~h Commun~ation~ Vo~ 2~ Supp~ment ~ 1988
P H A R M A C O L O G I C M A N I P U L A T I O N OF TUMOR C E L L IMMUNOGENICITY
(XENOGENIZATION)
AS A MEANS OF INDUCING T H E I R REJECTION IN EXPERIMENTAL IMMUNOTHERAPY
P. Puccetti, R. Bianchi, L. Romani, M.C. Fioretti Pharmacology Section, Dept. Exp. Med., University of Perugia Key words: Xenogenization, Mutagens, Immunotherapy Chemically xenogenized murine lymphomas carry novel antigenic determinants (drug-mediated tumor antigens or DMTA) responsible for their own rejection in histocompatible hosts and for protection against the original, poorly immunogenic cells when used as a tumor cell vaccine. Lymphocytes immune to xenogenized tumors are protective when adoptively transferred to naive recipient mice challenged with the original cells. Therefore, co-expression of DMTA and naturally occurring tumor antigens
(TATA) makes the latter suit-
able targets for potent antitumor immune responses. In the present communication we comparatively analyze the immune mechanisms triggered by DMTA and TATA, respectively, in antitumor immunotherapy models. In particular, we show that otherwise poorly immunogenic TATA, when coupled with DMTA, evoke a cellular immune response with the features of a delayed-type hypersensitivity reaction. This reaction involves induction of specifically immune T lymphocytes with the "helper" surface antigen phenotype, release of gamma interferon, and activation of tumoricidal macrophages in the host. Therefore, DMTA play a crucial role as adjuvant determinants in the triggering of TATA-specific antitumor responses that can be successfully ex ~ ploited in experimental models of tumor immunotherapy. DMTA, on the other hand, also induce specific responses that are primarily mediated by cytotoxic T lymphocytes and can be likewise used in immunotherapy protocols of xenogenized tumors grafted in deliberately immunodepressed recipient hosts. REFERENCES:
Puccetti P., Romani L. and Fioretti MC.
(1987) Cancer Metast. Rev. 6:93-111
Bianchi R., Romani L., Puccetti P. and Fioretti MC.
(1987) Int. J.
Cancer 40:7-11 Work supported by CNR-Italy grant N. 87.02806.44 within Progetto Finalizzato Oncologia.