title: T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies.
abstract: T-cell therapy with genetically modified T cells targeting CD19 or CD20 holds promise for the immunotherapy of hematologic malignancies. These targets, however, are only present on B cell-derived malignancies, and because they are broadly expressed in the hematopoietic system, their targeting may have unwanted consequences. To expand T-cell therapies to hematologic malignancies that are not B cell-derived, we determined whether T cells can be redirected to CD70, an antigen expressed by limited subsets of normal lymphocytes and dendritic cells, but aberrantly expressed by a broad range of hematologic malignancies and some solid tumors. To generate CD70-specific T cells, we constructed a chimeric antigen receptor (CAR) consisting of the CD70 receptor (CD27) fused to the CD3-ζ chain. Stimulation of T cells expressing CD70-specific CARs resulted in CD27 costimulation and recognition of CD70-positive tumor cell lines and primary tumor cells, as shown by IFN-γ and IL-2 secretion and by tumor cell killing. Adoptively transferred CD70-specific T cells induced sustained regression of established murine xenografts. Therefore, CD70-specific T cells may be a promising immunotherapeutic approach for CD70-positive malignancies.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Shaffer
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Yi
authors.forename: Kevin K H
authors.initials: KK
authors.lastname: Chow
authors.forename: Sunitha
authors.initials: S
authors.lastname: Kakarla
authors.forename: David M
authors.initials: DM
authors.lastname: Spencer
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
authors.forename: Meng-Fen
authors.initials: MF
authors.lastname: Wu
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Shannon
authors.initials: S
authors.lastname: Kenney
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
mesh_terms: D000818:Animals; D053282:CD27 Ligand / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
chemical_list: D053282:CD27 Ligand; D016207:Cytokines; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7