Chimeric antigen receptors for T cell immunotherapy: Current understanding and future directions Journal Article

Authors: Curran, K. J.; Pegram, H. J.; Brentjens, R. J.
Article Title: Chimeric antigen receptors for T cell immunotherapy: Current understanding and future directions
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. © 2012 John Wiley & Sons, Ltd.
Keywords: signal transduction; cancer chemotherapy; fludarabine; review; neoplasms; t lymphocyte; t-lymphocytes; interleukin 2; cancer immunotherapy; low drug dose; liver toxicity; breast cancer; tumor volume; epidermal growth factor receptor 2; cyclophosphamide; kidney carcinoma; gene transfer; prostate cancer; t lymphocyte receptor; lymphocyte activation; prostate specific membrane antigen; immunotherapy; antigens, neoplasm; recombinant fusion proteins; genetic engineering; receptors, antigen, t-cell; neuroblastoma; colon cancer; medical research; cell migration; adoptive cell therapy; chimeric antigen receptor; cell therapy; adoptive transfer; medical literature; hematopoietic stem cell; immunotherapy, adoptive; cd19 antigen; single chain fragment variable antibody; cd28 antigen; lymphocyte function; hla system; chimeric protein; gene transfer techniques; intracellular signaling; t cell; tumor microenvironment; clinical trial (topic); genes, t-cell receptor; genetic therapy
Journal Title: Journal of Gene Medicine
Volume: 14
Issue: 6
ISSN: 1099-498X
Publisher: John Wiley & Sons  
Date Published: 2012-06-01
Start Page: 405
End Page: 415
Language: English
DOI: 10.1002/jgm.2604
PROVIDER: scopus
PUBMED: 22262649
PMCID: PMC4697438
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 1 August 2012" - "CODEN: JGMEF" - "Source: Scopus"
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MSK Authors
  1. Renier J Brentjens
    195 Brentjens
  2. Kevin Joseph Curran
    58 Curran
  3. Hollie Jaine Pegram
    18 Pegram