title: A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies.
abstract: Options for targeted therapy of T-cell malignancies remain scarce. Recent clinical trials demonstrated that chimeric antigen receptors (CARs) can effectively redirect T lymphocytes to eradicate lymphoid malignancies of B-cell origin. However, T-lineage neoplasms remain a more challenging task for CAR T cells due to shared expression of most targetable surface antigens between normal and malignant T cells, potentially leading to fratricide of CAR T cells or profound immunodeficiency. Here, we report that T cells transduced with a CAR targeting CD5, a common surface marker of normal and neoplastic T cells, undergo only limited fratricide and can be expanded long-term ex vivo. These CD5 CAR T cells effectively eliminate malignant T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma lines in vitro and significantly inhibit disease progression in xenograft mouse models of T-ALL. These data support the therapeutic potential of CD5 CAR in patients with T-cell neoplasms.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.
authors.forename: Maksim
authors.identifier: http://orcid.org/0000-0001-7178-8163
authors.initials: M
authors.lastname: Mamonkin
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.
authors.forename: Rayne H
authors.identifier: http://orcid.org/0000-0002-0670-0599
authors.initials: RH
authors.lastname: Rouce
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.
authors.forename: Haruko
authors.identifier: http://orcid.org/0000-0002-9038-1710
authors.initials: H
authors.lastname: Tashiro
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014161:Transduction, Genetic; D018183:Transplantation Chimera; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D018956:CD5 Antigens; D011948:Receptors, Antigen, T-Cell