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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center - Bone Marrow Transplant Service, Department of Pediatrics, New York, NY, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Curran
authors.forename: Hollie J
authors.initials: HJ
authors.lastname: Pegram
authors.forename: Renier J
authors.initials: RJ
authors.lastname: Brentjens
mesh_terms: D019264:Adoptive Transfer; D000951:Antigens, Neoplasm / Q000235:genetics*; D018014:Gene Transfer Techniques; D019672:Genes, T-Cell Receptor; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins