Using monoclonal antibodies to stimulate antitumor cellular immunity.

Monoclonal antibodies (mAbs) have an established role in current cancer therapy with seven approved for the treatment of a wide variety of tumors. The approved mAbs directly target tumor cells; however, it is becoming increasingly clear that as well as their direct effects, these mAbs can present antigens to the immune system. This stimulates long-lasting T-cell immunity, which may correlate with long-term survival. A more direct approach is to use mAbs to target antigens directly to antigen-presenting cells. One approach, ImmunoBody, which has just entered the clinic, stimulates antitumor immunity using mAbs genetically engineered to express tumor-specific T-cell epitopes. T cells not only respond via their T-cell receptors recognizing T-cell epitopes presented on MHC but are also influenced by stimulation of a wide variety of costimulatory molecules. mAbs targeting these molecules can also influence antitumor immunity. The main protagonist in this class of mAbs is ipilimumab, which has recently been shown to improve survival at 2 years in 23% of advanced melanoma patients. Combinations of mAbs targeting tumor antigens to activated antigen-presenting cells and mAbs targeting costimulatory receptors may provide effective therapy for a broad range of tumors.