Mechanisms of action of therapeutic antibodies for cancer.
The therapeutic utility of antibodies and their derivatives is achieved by various means. The FDA has approved several targeted antibodies that disrupt signaling of various growth factor receptors for the treatment of a number of cancers. Rituximab, and other anti-CD20 monoclonal antibodies are active in B cell malignancies. As more experience has been gained with anti-CD20 monoclonal antibodies, the multifactorial nature of their anti-tumor mechanisms has emerged. Other targeted antibodies function to dampen inhibitory checkpoints. These checkpoint inhibitors have recently achieved dramatic results in several cancers, including melanoma. These and related antibodies continue to be investigated in the clinical and pre-clinical settings. Novel antibody structures that target two or more antigens have also made their way into clinical use. Tumor targeted antibodies can also be conjugated to chemo- or radiotherapeutic agents, or catalytic toxins, as a means to deliver toxic payloads to cancer cells. Here we provide a review of these mechanisms and a discussion of their relevance to current and future clinical applications.
Departments of Oncology and Internal Medicine, Georgetown University Medical Center and Lombardi Comprehensive Cancer Center, Washington, DC, United States.
J M
JM
Redman
Departments of Oncology and Internal Medicine, Georgetown University Medical Center and Lombardi Comprehensive Cancer Center, Washington, DC, United States.
E M
EM
Hill
Departments of Oncology and Internal Medicine, Georgetown University Medical Center and Lombardi Comprehensive Cancer Center, Washington, DC, United States.
D
D
AlDeghaither
Departments of Oncology and Internal Medicine, Georgetown University Medical Center and Lombardi Comprehensive Cancer Center, Washington, DC, United States. Electronic address: weinerl@georgetown.edu.
L M
LM
Weiner
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D060908:CTLA-4 Antigen; D066246:ErbB Receptors; D061026:Programmed Cell Death 1 Receptor; D018719:Erb-b2 Receptor Tyrosine Kinases
Antibodies; Immunoconjugates; Immunotoxins