期刊
JOURNAL OF GENE MEDICINE
卷 14, 期 6, 页码 405-415出版社
WILEY
DOI: 10.1002/jgm.2604
关键词
adoptive cell therapy; chimeric antigen receptor; immunotherapy; T cell
资金
- National Institutes of Health [CA-138738, CA-59350]
- Alliance for Cancer Gene Therapy
- Damon Runyon Clinical Investigator Award
- Annual Terry Fox Run for Cancer Research (New York, NY)
- Commonwealth Cancer Foundation for Research
- Experimental Therapeutics Center of MSKCC
- Geoffrey Beene Cancer Foundation
- William Lawrence and Blanche Hughes Foundation
- St Baldrick's Foundation Post Doctoral Fellowship in Childhood Cancer
Background The genetic engineering of T cells through the introduction of a chimeric antigen receptor (CAR) allows for generation of tumor-targeted T cells. Once expressed by T cells, CARs combine antigen-specificity with T cell activation in a single fusion molecule. Most CARs are comprised of an antigen-binding domain, an extracellular spacer/hinge region, a trans-membrane domain and an intracellular signaling domain resulting in T cell activation after antigen binding. Methods We performed a search of the literature regarding tumor immunotherapy using CAR-modified T cells to provide a concise review of this topic. Results This review aims to focus on the elements of CAR design required for successful application of this technology in cancer immunotherapy. Most notably, proper target antigen selection, co-stimulatory signaling, and the ability of CAR-modified T cells to traffic, persist and retain function after adoptive transfer are required for optimal tumor eradication. Furthermore, recent clinical trials have demonstrated tumor burden and chemotherapy conditioning before adoptive transfer as being critically important for this therapy. Future research into counteracting the suppressive tumor microenvironment and the ability to activate an endogenous anti-tumor response by CAR-modified T cells may enhance the therapeutic potential of this treatment. Conclusions In conclusion, CAR-modified T cell therapy is a highly promising treatment for cancer, having already demonstrated both promising preclinical and clinical results. However, further modification and additional clinical trials will need to be conducted to ultimately optimize the anti-tumor efficacy of this approach. Copyright (c) 2012 John Wiley & Sons, Ltd.
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