Therapeutic potential of anti-CD137 (4-1BB) monoclonal antibodies

INTRODUCTION: 4-1BB (CD137) is an important T-cell stimulating molecule. The 4-1BB mAb or its variants have shown remarkable therapeutic activity against autoimmunity, viral infections, and cancer. Antibodies to 4-1BB have recently entered clinical trials for the treatment of cancer with favorable toxicity profile. In this article, we present a review documenting the efficacy and pitfalls of 4-1BB therapy. AREAS COVERED: An extensive literature search has been made on 4-1BB, spanning two decades, and a comprehensive report is presented here highlighting the origins, biological effects, therapeutic potential, and mechanistic basis of targeting 4-1BB as well as the side effects associated with such therapy. EXPERT OPINION: Research so far indicates that 4-1BB is highly protective against various pathological conditions including cancer. However, a few important side effects of 4-1BB therapy such as liver toxicity, thrombocytopenia, anemia, and suppressive effects on certain immune competent cells should be taken into consideration before it is used for human therapy.