Journal
ANNUAL REVIEW OF MEDICINE, VOL 65
Volume 65, Issue -, Pages 333-347Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-med-060512-150254
Keywords
adoptive transfer; chimeric antigen receptor; gene transfer; synthetic biology; T cell receptor
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Funding
- NCI NIH HHS [R01 CA116660, P30 CA016520, R01 CA102646, P01 CA066726] Funding Source: Medline
- NIAID NIH HHS [P30 AI045008] Funding Source: Medline
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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.
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