Low doses of 105AD7 cancer vaccine preferentially stimulate anti-tumor T-cell immunity

Clinical studies with the human anti-idiotypic antibody 105AD7 have clearly shown that 791Tgp72 is a good target antigen for cell-mediated immunity. No antibody-related toxicity was observed in any of the 135 patients entered into phase I/II clinical trials of 105AD7, whereas both helper and cytotoxic T-cell responses were induced. The helper responses were exemplified by induction of interleukin-2 (1L-2), antigen-specific blastogenesis, and enhanced natural killer (NK) activity. Anti-tumor cytotoxicity was measured directly and was supported by activation of circulating CD8 cells. In this study, it is shown that a 100-mu g injection of 105AD7 was more effective than the 200-mu g dose. Enhanced IL-2 production was observed following 15/19 injections of 100 mu g of 105AD7 whereas only 4/11 injections of 200 mu g of 105AD7 induced responses (p <0.02). Similarly, time to progression was significantly (p <0.05) slower (median 6 m) in patients injected with 100 mu g than patients receiving the higher dose, suggesting that 100 mu g or lower may be the optimal dose. The standard dose for hepatitis vaccination is 10 mu g. In vitro blastogenesis assays on naive donors have shown that a dose of 105AD7, which is either too high or too low, fails to activate T cells. The optimal dose in vitro is 10 ng.