Mutagen-induced Imm+ variants: the need for viable and cloned Imm+ variants for effective protection against a primary murine tumor and its metastases
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Immunogenic variants (Imm+) generated after the treatment of murine tumor cells with the mutagenN-methyl-N′-nitro-N-nitrosoguanidine (MNNG) can produce a strong protective response against non-mutagenized parent tumor cells. The use of this methodology to treat human tumors is currently thwarted by technological difficulties in applying the findings obtained with murine models to human disease. Two of these difficulties are described in this study. The first is that Imm+ variants lose most of their immunogenicity after treatment with X-irradiation or mitomycin C. The second is that mutagen-treated tumor cells must be cloned so as to select for Imm+ variants, for the presence of as few as 0·001 per cent tumorigenic cells within the bulk population will result in the failure of the protective effect of the Imm+ variants.
Because of these and other difficulties with mutagen-induced Imm+ variants, we have developed a different approach to producing such variants using transfection of tumor cells with foreign genes. In contrast to mutagen induced Imm+ variants, these variants have been shown to retain their immunogenicity after X-irradiation.
KeywordsTumor Cell Protective Effect Human Disease Human Tumor Murine Model
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- Boon, T., 1985, Tum− variants: immunogenic variants obtained by mutagen treatment or tumor cells.Immunology Today,6, 307–311.Google Scholar
- Boon, T., andKellekman, O., 1977, Rejection by syngeneic mice of cell variants obtained by mutagenesis of a malignant teratocarcinoma line.Proceedings of the National Academy of Sciences U.S.A.,74, 272–275.Google Scholar
- Frost, P., andKerbel, R. S., 1986, Is the immunotherapy of metastasis feasible?Immunology and Cancer, edited by M. L. Kripke and P. Frost (Austin: University of Texas Press), p. 149.Google Scholar
- Frost, P., Kerbel, R. S., andTartamella-Biondo, R., 1981, Generation of highly metastatic tumors in DBA/2 mice: oncogenicity of A strain tumor cells.Invasion and Metastasis,1, 22–33.Google Scholar
- Frost, P., Prete, P., andKerbel, R. S., 1982, Eradication of thein vitro generation of the cytotoxic T cell response to a metastatic murine tumor: The role of suppressor T cells.International Journal of Cancer,20, 211–218.Google Scholar
- Frost, P., Sella, A., andHunt, B., 1987, The promises and problems of adapting mutagen induced Imm+ variants to the therapy of human metastases,Occult Nodal Metastasis in Solid Carcinoma, edited by P. J. Moloy and G. L. Nicolson (New York: Praeger Publishers),Cancer Research Monographs, Vol. 5, pp. 61–67.Google Scholar
- Hostetler, L. W., Ananthaswamy, H. N., andKripke, M. L., 1986, Generation of tumor-specific transplantation antigens by UV radiation can occur independently of neoplastic transformation.Journal of Immunology,137, 2721–2725.Google Scholar
- Kerbel, R. S., Twiddy, R. R., andRobertson, D. M., 1978, Induction of a tumor with greatly increased metastatic growth potential by injection of cells from a low metastatic H-2 heterozygous tumor cell line into an H-2 incompatible parental strain.International Journal of Cancer,22, 583–594.Google Scholar
- Peppoloni, S., Herberman, R., andGorelik, E., 1984, Induction of highly immunogenic variants of 3LL tumor by UV irradiation.Cancer Research,45, 2560–2564.Google Scholar