title: Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells.
abstract: Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors. CAR-T treatment has emerged as a promising approach for patients with hematological malignancies, and there are several works reporting clinical trials of the use of CAR-modified T-cells in acute lymphoblastic leukemia, chronic lymphoblastic leukemia, multiple myeloma, lymphoma, and in acute myeloid leukemia by targeting different antigens. This review reports the history of adoptive immunotherapy using CAR-Ts, the CAR-T manufacturing process, and T cell therapies in development for hematological malignancies.
authors.affiliation: Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età evolutiva, University of Messina, Messina, Italy. Electronic address: aallegra@unime.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Allegra
authors.affiliation: Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età evolutiva, University of Messina, Messina, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Innao
authors.affiliation: Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età evolutiva, University of Messina, Messina, Italy.
authors.forename: Demetrio
authors.initials: D
authors.lastname: Gerace
authors.affiliation: Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età evolutiva, University of Messina, Messina, Italy.
authors.forename: Doriana
authors.initials: D
authors.lastname: Vaddinelli
authors.affiliation: Division of Hematology, Dipartimento di Patologia Umana dell'Adulto e dell'Età evolutiva, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy*; D049674:History, 21st Century; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000266:history / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies
keywords: Acute lymphoblastic leukemia; Adoptive immunotherapy; Cancer immunotherapy; Chimeric antigen receptor-modified T cells; Hematological malignancies