Combination antibody-based cancer immunotherapy

It is now commonly recognized that tumor-targeting monoclonal antibodies (mAb) demonstrate significant therapeutic effects in cancer patients. Multiple effector mechanisms are involved in the primary response; however, the induction of tumor-specific immunity has sometimes been a desired outcome and in some cases has contributed to the success of mAb-based therapy. Initiating the antitumor immune response by creating a tumor antigen supply from dying (apoptotic) tumor cells is a goal of tumor-targeting mAb therapy, and ideally a sufficiently immunogenic tumor cell death might provide a platform on which combination immunotherapies can be based. In this review, the authors discuss the possible utility and pitfalls of using such a therapy, which combines tumor cell death with immune activation therapy. The ideas are largely based on the observation that three-mAb (anti-DR5 mAb, anti-CD40 mAb, and anti-CD137 mAb [trimAb]) therapy has been shown to be very effective in a number of mouse experimental tumor models. The authors believe that this rational activation and inhibition of key points in the immune response can be an effective strategy to apply in human cancer patients.