Immune Functions of Tumor Cell Variants

Fuji, Hiroshi

Abstract

The long-range goal of this study is to provide new and rational approches aimed at facilitation of the host's immune defense against tumors. The short-range goals of the study are to establish variant lines of the DBA/2 mouse L1210 cells, which express differences in the amounts or the kinds of tumor-associated antigen (TAA) and/or normal cell surface antigens, and to study their immunogenicity and immunoregulatory functions. The existing drug-resistant L1210 sublines that express high amounts of the TAA will also be used. We will study: (1) whether variant cells with low TAA density elicit stronger suppressor cell activity than those with high TAA density; (2) whether variant cells differing in TAA elicit different types of host responses; or (3) whether differences in the density of normal surface antigens affect the ability of variant cells to elicit host responses. Antigenic properties of variant lines will be thoroughly analyzed with monospecific and monoclonal antibodies directed to the TAA. We have demonstrated variation among L1210 clones derived by limiting dilution in their susceptibility to specific T cell-mediated cytotoxicity (TC), which is inversely related to tumorigenicity in syngeneic animals. Thus, although a majority of such clones were TC resistant and highly tumorigenic, some clones were TC susceptible and nontumorigenic. Moreover, an inoculation of the variant clones bearing the latter phenotype was shown to elicit protective immunity in host mice against a challenge with the parent L1210 cell line. In our recent experiments in vitro, it was shown that such nontumorigenic variant clones were more efficient in eliciting the specific TC responses in spleen cell cultures than the tumorigenic clones. (MI)