Fast-tracked CTL: Rapid induction of potent anti-tumor killer T cells in situ

Current strategies to elicit cytolytic T cell responses specific for tumor-associated or over-expressed self antigens rely on multiple immunizations and in vitro expansion schemes. Here we report the in vivo induction of activated tumor-specific CD8⁺ CTL just 6 days after treatment with the IgM immune modulator B7-DC XAb. Antibody treatment of mice at the time of tumor challenge elicited potent CTL with a specificity that distinguished between MHC-compatible tumors. Remarkably, these effector cells were not generated by the extensive proliferation of naive CTL precursors, though their induction required CD4⁺ T cell help and classical B7 costimulatory signals. Tumor targets were recognized and lysed in an MHC-restricted, perforin-dependent manner, indicating that these rapidly induced effectors resemble traditionally defined CTL, despite the finding that strong increases in the expression of the effector/memory marker CD44 and the activation marker CD69 were not elicited. These CTL were induced in animals bearing well-established tumors and resulted in anti-tumor protection, underscoring the therapeutic potential of this type of effector T cell population in cancer patients.