Protection against transplanted and spontaneous lymphoma by inoculation of heat-altered syngeneic tumor cells in splenectomized mice (original) (raw)
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European Journal of Immunology, 1976
Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells* Incubation of spleen cells from mice having rejected a Moloney sarcoma virus (MSV)-induced tumor with syngeneic irradiated lymphoma or sarcoma cells bearing MSV-associated antigens in secondary mixed leukocyte-tumor cell cultures (MLTC) resulted in the generation of highly active cytolytic T lymphocytes (CTL) specifically directed against syngeneic target cells bearing MSV-associated antigens. When MSV-immune spleen cells from C57BL/6 (H-2b) and BALB/c (H-2d) mice were compared with respect to their ability t o generate CTL in syngeneic secondary MLTC, it was found that both lymphoid cell populations were equally able t o mount an anamnestic CTL response to MSV-associated antigens as assessed by a short-term 51Cr release assay. However, quantitative analysis of the activity of both CTL populations on either H-2b or H-2d tumor cells indicated that target cells sharing the same major histocompatibility complex (MHC) as the effector cells were lysed 10-to 100-fold more efficiently than allogeneic target cells. As suggested by the results of inhibition experiments using mixtures of 51 Cr-labeled and unlabeled target cells, preferential lysis of syngeneic versus allogeneic tumor cells might be related to the establishment of effective adhesions between the former and CTL. Direct evidence for the role of MHC in determining the antigenic specificity of CTL directed against MSV-associated antigens was provided by results obtained using MSV-immune spleen cells from congenic resistant mice. Furthermore, studies of the response of F , (H-2b/d) hybrid mice showed that stimulation of immune spleen cells with tumor cells from one parental strain or the other in secondary MLTC resulted in the generation of CTL capable of lysing tumor target cells of the same parental strain as the stimulating cells, but not of the other. The results thus suggested the presence of two sets of CTL precursor cells in F, MSV-immune spleens, each set responding exclusively to tumor antigens associated with only one of the two parental phenotypes.
On the immunostimulatory hypothesis of cancer
Medicina, 2011
There is a rather generalized belief that the worst possible outcome for the application of immunological therapies against cancer is a null effect on tumor growth. However, a significant body of evidence summarized in the immunostimulatory hypothesis of cancer suggests that, upon certain circumstances, the growth of incipient and established tumors can be accelerated rather than inhibited by the immune response supposedly mounted to limit tumor growth. In order to provide more compelling evidence of this proposition, we have explored the growth behavior characteristics of twelve murine tumors -most of them of spontaneous origin- arisen in the colony of our laboratory, in putatively immunized and control mice. Using classical immunization procedures, 8 out of 12 tumors were actually stimulated in "immunized" mice while the remaining 4 were neither inhibited nor stimulated. Further, even these apparently non-antigenic tumors could reveal some antigenicity if more stringent ...
European Journal of Immunology, 1978
Immune responses to weakly immunogenic virally induced tumors 1. Overcoming low responsiveness by priming mice with a syngeneic in vitro tumor line or allogeneic cross-reactive tumor* This report describes model systems which show low primar:, in virro syngeneic cytotoxic responses t o a Moloney-induced YAC tumor (syngeneic in A mice) and a Rauscher-induced RBLS tumor (syngeneic in CS7BL/6 mice) and examines different approaches t o overcome these defects. Two major findings were obtained: (a) spleen cells from A mice, injected with tumor cells from an in vitro tumor line YAC-1, derived from YACL, could generate a significant syngeneic cytotoxic response. In contrast, spleen cells from A mice injected with tumor cells from the in vivo tumor line failed t o generate a syngeneic cytotoxic response. Thus, tumor cells from the in vitro line were more immunogeneic that those from the in vivo line. (b) Spleen cells from A mice which were injected with the crossreactive allogeneic tumor RBLS, could generate significant cytotoxic responses t o the syngeneic tumors YAC and YAC-1. Similarly, spleen cells from CS7BL/6 mice injected with the cross-reactive allogeneic tumor YAC-1, could generate a significant cytotoxic response t o the syngeneic tumor RBLS. Thus, Cross-reactive allogeneic tumors could stimulate syngeneic cytotoxicity. The theoretical and the practical implications of these studies are discussed.
Immunization in tumor prevention
International Immunopharmacology, 2003
Recent experimental data suggest that immunity can be activated to prevent tumors. The rationale for prevention is strong because the setting is one endowed with an immune system that is neither impaired by tumor and treatment-induced suppression, nor tolerant to tumor-associated antigens. Oncogenic growth factor receptors are tumor antigens and rational targets for specific immunoprevention. Successful prevention of mammary carcinomas in Her-2/neu transgenic mice is cited as an evidence of the validity of this approach. The specific properties of the Her-2/neu gene product as an antigen and the nature of the immune responses induced by effective preventive treatments are summarized. D
Immunization against a dominant tumor antigen abrogates immunogenicity of the tumor
Cancer immunity, 2002
To study the role of subdominant epitopes in tumor rejection we have used EL4 tumor cells and their ovalbumin (OVA)-transfected counterpart E.G7. Immunization of mice with irradiated EL4 cells conferred protection against challenge with EL4 and E.G7. Surprisingly, immunization with irradiated E.G7 cells did not protect against a subsequent challenge with EL4 or E.G7. Growth of E.G7 tumors in E.G7 immunized mice was not due to loss of expression of OVA or MHC I by the tumor cells in vivo. Adoptive transfer of OVA-specific transgenic T cells, immunization of mice with native or heat-denatured OVA or infection with a recombinant virus expressing OVA also failed to induce rejection of E.G7 tumors. Lack of immunogenicity of the OVA-expressing tumor could not be overcome by combination of a CD40 activating antibody with immunization against E.G7 or OVA. Our results suggest that immunization against subdominant epitopes is more effective than vaccination against dominant epitopes.
Regulation of the immune response to tumor antigen
Cellular Immunology, 1980
We present evidence for a role of I-A subregion-encoded determinants in syngeneic tumor immunity. In animals rendered immune to the S1509a fibrosarcoma, daily treatment with microliter quantities of antisera directed against Kk and I-Ak determinants expressed on lymphoid cells of host origin decreased the capacity for immune tumor rejection. Absorption studies revealed that anti-I-Ak antibody activity alone was sufficient for the manifestation of this effect. Furthermore, experiments utilizing F1 hybrids showed that an antiserum that was genetically unable to interact with H-2 determinants expressed on the tumor was equally effective in inhibiting tumor immunity. Suggestive evidence that the activity of this antiserum is related to interference with the generation of effector T cell function was provided by the observation that hyperimmune animals pretreated with an anti-KkI-Ak antiserum were no longer capable of adoptively transferring tumor immunity to naive recipients. Thus, it is possible to regulate the secondary immune response to tumor antigens by using antisera with specificity for I-A determinants expressed on cells or possibly on factors of the host lymphoid system.