title: Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer.
abstract: BACKGROUND
  Chimeric antigen (or antibody) receptors (CAR) are fusion proteins typically combining an antibody-derived targeting fragment with signaling domains capable of activating immune cells. Recent clinical trials have shown the tremendous potential of adoptive cell transfer (ACT) of autologous T cells engineered to express a CD19-specific CAR targeting B-cell malignancies. Building on this approach, ACT therapies employing allogeneic CAR-expressing cytotoxic cells are now being explored.
  
  
  METHODS
  The basic principles of CAR-ACT are introduced. The potential benefits as well as problems of using allogeneic CAR-modified cells against tumor antigens are discussed. Various approaches to allogeneic CAR therapy are presented, including donor leukocyte infusion, CAR-redirected γδ T cells and natural killer cells, strategies to avoid graft-versus-host disease, modulation of lymphocyte migration, and exploitation of graft-versus-host reactivity.
  
  
  CONCLUSIONS
  CAR-modified allogeneic cells have the potential to act as universal effector cells, which can be administered to any patient regardless of MHC type. Such universal effector cells could be used as an 'off-the-shelf' cell-mediated treatment for cancer.
authors.affiliation: University of California, Department of Molecular and Cell Biology, Cancer Research Laboratory Berkeley , Berkeley, CA 94720-3200 , USA.
authors.forename: Assaf
authors.initials: A
authors.lastname: Marcus
authors.forename: Zelig
authors.initials: Z
authors.lastname: Eshhar
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000941:Antigens / Q000276:immunology; D018941:Antigens, CD19 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
chemical_list: D000941:Antigens; D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins
keywords: CD19; FTY720; T-cell receptor disruption; adoptive cell transfer; allogeneic; cancer; chimeric antigen receptors; egress; graft-versus-host disease; graft-versus-tumor; her2/neuregulin; host-versus-graft; t-body; tumor