title: Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells?
abstract: Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such 'on-target off-tumor' toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Areas covered: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field. Expert commentary: Targeting an activation associated antigen which is transiently expressed by stem cells seems to be safe, like CAR T cells targeting CD30 spare CD30+hematopoietic stem and progenitor cells while eliminating CD30+lymphoma cells, whereas targeting lineage associated antigens which increase in expression during cell maturation, like folate receptor-β and CD123, is of risk to destruct tissue stem cells.
authors.affiliation: a Center for Molecular Medicine Cologne , University of Cologne , Cologne , Germany.|b Department I of Internal Medicine , University Hospital Cologne , Cologne , Germany.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Hombach
authors.affiliation: a Center for Molecular Medicine Cologne , University of Cologne , Cologne , Germany.|b Department I of Internal Medicine , University Hospital Cologne , Cologne , Germany.
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
mesh_terms: D053687:Adult Stem Cells / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000639:trends; D018716:Molecular Mimicry; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Adoptive cell therapy; CAR; CD123; CD30; HSPCs; SP6/PI9; T cell; chimeric antigen receptor; hematopoietic stem and progenitor cell; stem cell