title: T cells expressing CD19-specific Engager Molecules for the Immunotherapy of CD19-positive Malignancies.
abstract: T cells expressing chimeric antigen receptors (CARs) or the infusion of bispecific T-cell engagers (BITEs) have shown antitumor activity in humans for CD19-positive malignancies. While BITEs redirect the large reservoir of resident T cells to tumors, CAR T cells rely on significant in vivo expansion to exert antitumor activity. We have shown that it is feasible to modify T cells to secrete solid tumor antigen-specific BITEs, enabling T cells to redirect resident T cells to tumor cells. To adapt this approach to CD19-positive malignancies we now generated T cells expressing secretable, CD19-specific BITEs (CD19-ENG T cells). CD19-ENG T cells recognized tumor cells in an antigen-dependent manner as judged by cytokine production and tumor killing, and redirected bystander T cells to tumor cells. Infusion of CD19-ENG T cells resulted in regression of leukemia or lymphoma in xenograft models and a survival advantage in comparison to control mice. Genetically modified T cells expressing engager molecules may present a promising addition to current CD19-targeted immunotherapies.
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mireya Paulina
authors.initials: MP
authors.lastname: Velasquez
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Torres
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Kota
authors.initials: K
authors.lastname: Iwahori
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Kakarla
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Arber
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Tania
authors.initials: T
authors.lastname: Rodriguez-Cruz
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Arpad
authors.initials: A
authors.lastname: Szoor
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Challice L
authors.initials: CL
authors.lastname: Bonifant
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gerken
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
mesh_terms: D000072283:A549 Cells; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007167:Immunotherapy; D020014:K562 Cells; D051379:Mice; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D057127:Single-Chain Antibodies / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; D057127:Single-Chain Antibodies