Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions - PubMed (original) (raw)

Review

Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions

Kevin J Curran et al. J Gene Med. 2012 Jun.

Abstract

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 © 2012 John Wiley & Sons, Ltd.

PubMed Disclaimer

Figures

Figure 1

Figure 1. Considerations for effective CAR modified T cell Immunotherapy

Successful application of CAR modified T cell immunotherapy requires the consideration of several qualities, including the CAR design, tumor microenvironment, patient clinical status, and funding mechanisms required for CAR development and clinical trials.

Comment in

Similar articles

Cited by

References

    1. Weiden PL, Sullivan KM, Flournoy N, et al. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. The New England journal of medicine. 1981;304:1529–1533. doi: 10.1056/NEJM198106183042507. - DOI - PubMed
    1. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112:4371–4383. doi: 10.1182/blood-2008-03-077974. - DOI - PubMed
    1. Rosenberg SA, Restifo NP, Yang JC, et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nature reviews Cancer. 2008;8:299–308. doi: 10.1038/nrc2355. - DOI - PMC - PubMed
    1. Sadelain M, Riviere I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nature reviews Cancer. 2003;3:35–45. doi: 10.1038/nrc971. - DOI - PubMed
    1. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86:10024–10028. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources