ABSTRACT
By mutagenesis of a cell line derived from Lewis lung carcinoma (3LL), it is possible to obtain at high frequency stable tumor cell variants (tum-) that are rejected by syngeneic mice. The possibility of obtaining a cytolytic T cell (CTL) response directed specifically against these tum- variants was examined. With the four variants that were analysed, a significant cytolytic activity was obtained with peritoneal cells from immune mice collected shortly after an intraperitoneal boost and also with spleen cells after a secondary stimulation in vitro. The CTL populations preferentially lysed the immunizing tum- variant, while also showing a cross-reactive lysis against the other variants and the original 3LL cells. Highly active CTL clones could be isolated from limiting dilution microcultures of these CTL populations. The clonal analysis clearly showed the existence of two distinct CTL populations, one directed exclusively against the immunizing variant and another that lysed all 3LL targets equally. This CTL specificity analysis therefore demonstrates directly the presence of new antigens on the 3LL tum- cell variants.
Subject(s)
Antigens, Neoplasm/immunology , Lung Neoplasms/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Cell Line , Clone Cells/immunology , Epitopes , Methylnitronitrosoguanidine/pharmacology , Mice , Mice, Inbred C57BL , Neoplasm Transplantation , Neoplasms, Experimental/immunologyABSTRACT
It has been reported that, by mutagenesis of a malignant mouse teratocarcinoma cell line, it is possible to obtain cell variants that are incapable of forming progressive tumors in syngeneic mice. These variants, which were called "tum-," are eliminated from the host by an immune rejection process. We report here that similar variant cell clones can be obtained at high frequency from a Lewis lung carcinoma cell line treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Syngeneic C57BL/6 mice reject these tum- clones and acquire a strong radioresistant immune protection against the immunizing clone. When the challenging tum- clone differs from the immunizing clone, a weaker radioresistant immune protection can be demonstrated with some, but not all, combinations. All the tum- clones induce a significant protection against the original Lewis lung malignant cells. These results imply that each Lewis lung tum- variant carries on its surface a singular antigen in addition to one or more weak antigens already present on the original tumor cell line. This antigenic pattern is similar to that found on teratocarcinoma tum- variants. Our results suggest that the procedure of using a mutagen in order to generate tum- variants carrying new transplantation antigens may be generally applicable to cancer cells.
