Antibody-based therapy for solid tumors.
Monoclonal antibodies have emerged as a class of novel oncology therapeutics. The selectivity and specificity, the unique pharmacokinetics, and the ability to engage and activate the immune system differentiate these biologics from traditional small molecule anticancer drugs. In this review, we focus on 4 antibodies approved for clinical use in treating solid tumors, trastuzumab (Herceptin) for breast cancer, bevacizumab (Avastin) for colorectal cancer and non-small cell lung cancer, cetuximab (Erbitux) for colorectal cancer and head and neck cancer, and panitumumab (Vectibix) for colorectal cancer. The anticancer effects of these antibodies derive from blockade of growth factor/receptor interaction and/or down-regulation of oncogenic proteins (eg, growth factor receptors) on the tumor cell surface, and for some of these antibodies from the ability to elicit effector mechanisms of the immune system, such as antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity. The mechanism behind each antibody, the registration trials for their approved indications, and emerging indications are the focus of this article. We also review clinical considerations including commonly observed and antibody-related side effects, and dosing schedules. In addition, perspectives on challenges and opportunities of oncology antibody clinical development, antibody engineering, and the use of pharmacogenomics are presented.
Yan
Li
L
Clinical and Quantitative Sciences, Merck Research Laboratories, North Wales, Pennsylvania 19454-1099, USA.
Hsu
Karl
K
Beckman
Robert A
RA
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D010597:Pharmacogenetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000187:drug effects; D000068878:Trastuzumab
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007155:Immunologic Factors; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; C485206:pertuzumab; D000068878:Trastuzumab