title: Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies.
abstract: Chimeric T-cell receptors (ChTCR), are a fascinating technological step in the field of immunotherapy for orienting the activity of immune cells towards specific molecular targets expressed on the cell surface of various tumors, including hematologic malignancies. The main characteristics of ChTCR are their ability to redirect T-cell specificity and their killing/effector activity toward a selected target in a non MHC-restricted manner, exploiting the antigen binding properties of monoclonal antibodies. ChTCR are, in fact, artificial T-cell receptors constituted by an antigen-recognizing antibody molecule linked to a T-cell triggering domain. Various hematologic malignancies represent optimal targets for the exploitation of ChTCR, because of the bright expression of specific antigens on the surface of tumor cells. Thus, CD19 and CD20 have been targeted for B-cell lymphoid tumors (acute lymphoblastic leukemia-ALL, lymphomas and chronic lymphocytic leukemia-CLL), CD33 for myeloid leukemia, and CD30 for lymphomas. Even though technical and safety progresses are still needed to improve the profile of gene transfer and protein expression of ChTCR, phase 1 trials will be carried out in the near future to demonstrate the feasibility of their clinical translation and, it is be hoped, give preliminary indications about their anti-tumor efficacy.
authors.affiliation: Centro di Ricerca Matilde Tettamanti, Department of Pediatrics, University of Milano-Bicocca, San Gerardo Hospital, Monza, Milan, Italy. ettore.biagi@pediatriamonza.it
authors.forename: Ettore
authors.initials: E
authors.lastname: Biagi
authors.forename: Virna
authors.initials: V
authors.lastname: Marin
authors.forename: Greta Maria Paola
authors.initials: GM
authors.lastname: Giordano Attianese
authors.forename: Erica
authors.initials: E
authors.lastname: Dander
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Amico
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D002648:Child; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D005544:Forecasting; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D017730:Ki-1 Antigen / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D063268:Sialic Acid Binding Ig-like Lectin 3; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; C571163:CD33 protein, human; D017730:Ki-1 Antigen; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3