Cytotoxic T-cell precursors against non-immunogenic rat tumors: limiting dilution analysis

After in vitro stimulation of lymphocytes with syngeneic tumor cells in the presence of interleukin 2 (IL-2), a cytotoxic T-cell response was observed against these spontaneously arising BDX tumors, which are non-immunogenic in the syngeneic host. The response was due to cytotoxic T-cells (CTL), which were specific for syngeneic tumor cells, i.e. neither syngeneic lymphoblasts, allogeneic lymphoblasts, allogeneic tumor cells, nor NK targets were lysed. The frequencies of anti-tumor lymph-node (LN) and spleen CTL precursors (CTLp) against a panel of syngeneic tumors of different histology varied between 1/6,000 and 1/16,000. Further analysis of the reactivity pattern of anti-tumor CTL revealed some degree of cross-reactivity within the syngeneic system. By a limiting dilution (LD) split culture approach in combination with cold target (CT) inhibition, it could be shown that tumors carry a panel of tumor-associated antigens (TAAs). Some tumors express individually specific as well as cross-reactive TAAs, while others carry cross-reactive TAAs only.