title: An oxygen sensitive self-decision making engineered CAR T-cell.
abstract: A key to the success of chimeric antigen receptor (CAR) T-cell based therapies greatly rely on the capacity to identify and target antigens with expression restrained to tumor cells. Here we present a strategy to generate CAR T-cells that are only effective locally (tumor tissue), potentially also increasing the choice of targetable antigens. By fusing an oxygen sensitive subdomain of HIF1α to a CAR scaffold, we generated CAR T-cells that are responsive to a hypoxic environment, a hallmark of certain tumors. Along with the development of oxygen-sensitive CAR T-cells, this work also provides a basic framework to use a multi-chain CAR as a platform to create the next generation of smarter self-decision making CAR T-cells.
authors.affiliation: Cellectis Inc, 430E, 29th street, NYC, NY 10016, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Juillerat
authors.affiliation: Cellectis, 8 rue de la croix Jarry, 75013, Paris.
authors.forename: Alan
authors.initials: A
authors.lastname: Marechal
authors.affiliation: Cellectis, 8 rue de la croix Jarry, 75013, Paris.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Filhol
authors.affiliation: Cellectis, 8 rue de la croix Jarry, 75013, Paris.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Valogne
authors.affiliation: Cellectis Inc, 430E, 29th street, NYC, NY 10016, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Valton
authors.affiliation: Cellectis, 8 rue de la croix Jarry, 75013, Paris.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Duclert
authors.affiliation: Cellectis, 8 rue de la croix Jarry, 75013, Paris.
authors.forename: Philippe
authors.initials: P
authors.lastname: Duchateau
authors.affiliation: Cellectis, 8 rue de la croix Jarry, 75013, Paris.
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirot
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005818:Genetic Engineering; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010100:Oxygen / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology* / Q000637:transplantation; D059016:Tumor Microenvironment
chemical_list: D000951:Antigens, Neoplasm; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D010100:Oxygen