Special Section on Cancer Gene Therapy
Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions
Article first published online: 27 JUN 2012
Copyright © 2012 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 14, Issue 6, pages 405–415, June 2012
How to Cite
Curran, K. J., Pegram, H. J. and Brentjens, R. J. (2012), Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J. Gene Med., 14: 405–415. doi: 10.1002/jgm.2604
- Issue published online: 27 JUN 2012
- Article first published online: 27 JUN 2012
- Accepted manuscript online: 19 JAN 2012 09:40PM EST
- Manuscript Accepted: 5 JAN 2012
- Manuscript Received: 8 NOV 2011
- adoptive cell therapy;
- chimeric antigen receptor;
- T cell
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.
We performed a search of the literature regarding tumor immunotherapy using CAR-modified T cells to provide a concise review of this topic.
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.
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 © 2012 John Wiley & Sons, Ltd.