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.