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.
Takeda
Kazuyoshi
K
Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan. ktakeda@med.juntendo.ac.jp
Okumura
Ko
K
Smyth
Mark J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000009:adverse effects; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects / Q000379:methods* / Q000639:trends
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm