Development of antibody-based therapeutics for oncology indications

Monoclonal antibodies have emerged as novel oncology therapeutics. These biologics exert anticancer effects via a variety of mechanisms of action including modulating the function of key regulatory molecules and signaling pathways of tumor cells such as blocking growth factor/receptor interaction and/or down-regulating expression of oncogenic proteins (e.g., growth factor receptors) on the cell surface; recruiting effector mechanisms of the immune system, such as anti body-dependent cellular cytotoxicity and complement-mediated cytotoxicity; as a targeting device in immnuoconjugates; and other mechanisms such as anti-idiotype, catalytic antibodies, or antibodies that modulate patient's immune responses to tumors. In this review, we focus on the research and development experience of four such representative antibody therapeutics, rituximab (Rituxan (R)), trastuzumab (Herceptin (R)), cetuximab (Erbitux (R)), and bevacizumab (Avastin (R)), approved for treating non-Hodgkin's lymphoma, metastatic breast cancer, and colorectal cancer, respectively. The biology behind each antibody target, their proposed mechanisms of action, as well as preclinical and clinical development of these antibodies are the topics of this article. Experience drawn from the development process of these four antibodies is instrumental for ongoing and future antibody development activities. In addition, perspective views on challenges and opportunities of oncology antibody therapeutics are presented.