Clinical evidence that the human monoclonal anti-idiotypic antibody 105AD7, delays tumor growth by stimulating anti-tumor T-cell responses.

Abstract

A human monoclonal anti-idiotypic antibody, 105AD7, which mimics a colorectal tumor associated antigen, 791Tgp72, has been developed. A Phase I trial in advanced colorectal cancer patients showed that 105AD7 therapy was nontoxic and that immunised patients had prolonged survival when compared to a contemporary group of patients treated in the same center. There is accumulating clinical evidence that 105AD7 delays tumor growth by stimulating anti-tumor T-cell responses. Stimulation of helper T-cells was exemplified in the phase I study as 105AD7 immunized patients showed antigen specific T-cell blastogenesis responses and enhanced IL-2 production. Further evidence was obtained from a new clinical study in which colorectal cancer patients were immunized prior to tumor resection. Immune infiltrating cells were analysed by immunohistochemistry and effector cell function was studied in immune cells from peripheral blood and tumor draining lymph nodes. Both activated CD4 and natural killer (NK) cells were observed at the tumor site, which is of interest as NK cells are rarely found in colorectal tumors. Effector studies confirmed that NK activity was enhanced in 3/6 patients. Increased autologous tumor killing was also found in 3/4 patients and accumulation of CD8RO cells following 105AD7 immunization also suggested that CD8 T cells were being stimulated.