title: Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy.
abstract: BACKGROUND
  Chimeric antigen receptors (CARs) usually combine the antigen binding site of a monoclonal antibody with the signal activating machinery of a T cell, freeing antigen recognition from MHC restriction and thus breaking one of the barriers to more widespread application of cellular therapy. Similar to treatment strategies employing monoclonal antibodies, T cells expressing CARs are highly targeted, but additionally offer the potential benefits of active trafficking to tumor sites, in vivo expansion and long-term persistence. Furthermore, gene transfer allows the introduction of countermeasures to tumor immune evasion and of safety mechanisms.
  
  
  METHODS
  The basic structure of so-called first and later generation CARs and their potential advantages over other immune therapy systems. How these molecules can be grafted into immune cells (including retroviral and non-retroviral transduction methods) and strategies to improve the in vivo persistence and function of immune cells expressing CARs. Examples of tumor-associated antigens that have been targeted in preclinical models and clinical experience with these modified cells. Safety issues surrounding CAR gene transfer into T cells and potential solutions to them.
  
  
  CONCLUSIONS
  Because of recent advances in immunology, genetics and cell processing, CAR-modified T cells will likely play an increasing role in the cellular therapy of cancer, chronic infections and autoimmune disorders.
authors.affiliation: Center for Cell and Gene Therapy, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. caramos@bcm.edu
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Ramos
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D019139:Tumor Escape
chemical_list: D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins