Chimeric Antigen Receptor Therapy for Cancer

• Published in: Annual review of medicine 2014-01, Vol.65 (1), p.333-347
• Main Authors: Barrett, David M, Singh, Nathan, Porter, David L, Grupp, Stephan A, June, Carl H
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Cancer therapies; Cell Engineering; chimeric antigen receptor; Clinical trials; Cytotoxicity; gene transfer; Humans; Immunology; Immunotherapy - methods; Lymphocytes, Tumor-Infiltrating; Neoplasms - immunology; Neoplasms - therapy; Receptors, Antigen, T-Cell; synthetic biology; T cell receptor; T cell receptors; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - transplantation; Tumors
• ISSN: 0066-4219; 1545-326X
• DOI: 10.1146/annurev-med-060512-150254

Improved outcomes for patients with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, synthetic biology, and cell-processing technologies has paved the way for clinical applications of chimeric antigen receptor-based therapies. This new form of targeted immunotherapy merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and on elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer.