title: Challenges and opportunities of allogeneic donor-derived CAR T cells.
abstract: OBJECTIVE
  As T cells engineered with chimeric antigen receptors (CARs) are entering advanced phases of clinical trial testing with promising results, the potential implications of use in an allogeneic environment are emerging as an important consideration. This review discusses the use of allogeneic CAR therapy, the potential effects of T-cell receptor (TCR) signaling on CAR T-cell efficacy, and the potential for TCR elimination to generate an off-the-shelf product.
  
  
  RESULTS
  The majority of preclinical and clinical data regarding allogeneic T cells are focused on safety of their use given the potential for graft-versus-host disease (GVHD) mediated by the T-cell receptor expressed with the introduced CAR. Recent clinical trials using donor-derived CAR T cells are using either rigorous patient selection or T-cell selection (such as enrichment for virus-specific T cells). Although no GVHD has been reported, the efficacy of the allogeneic CAR treatment needs to be optimized. Several preclinical models limit allogeneic CAR-driven GVHD by utilizing memory T-cell selection, virus-specific T cells, gene-editing techniques, or suicide gene engineering.
  
  
  CONCLUSIONS
  In the allogeneic environment, the potential effects of TCR signaling on the efficacy of CAR could affect the clinical responses with the use of donor-derived CAR T cells. Better understanding of the functionality of donor-derived T cells for therapy is essential for the development of universal effector cells for CAR therapy.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Georgetown University.
authors.forename: Yinmeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elad
authors.initials: E
authors.lastname: Jacoby
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Fry
mesh_terms: D046148:Donor Selection; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D011948:Receptors, Antigen, T-Cell