title: Engager T cells: a new class of antigen-specific T cells that redirect bystander T cells.
abstract: Adoptive immunotherapy with antigen-specific T cells has shown promise for the treatment of malignancies. However, infused T cells are unable to redirect resident T cells, limiting potential benefit. While the infusion of bispecific T-cell engagers can redirect resident T cells to tumors, these molecules have a short half-life, and do not self amplify. To overcome these limitations, we generated T cells expressing a secretable T-cell engager specific for CD3 and EphA2, an antigen expressed on a broad range of human tumors (EphA2-ENG T cells). EphA2-ENG T cells were activated and recognized tumor cells in an antigen-dependent manner, redirected bystander T cells to tumor cells, and had potent antitumor activity in glioma and lung cancer severe combined immunodeficiency (SCID) xenograft models associated with a significant survival benefit. This new class of tumor-specific T cells, with the unique ability to redirect bystander T cells, may be a promising alternative to current immunotherapies for cancer.
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Kota
authors.initials: K
authors.lastname: Iwahori
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA [3] Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Kakarla
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA [3] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mireya P
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, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zongzhen
authors.initials: Z
authors.lastname: Yi
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gerken
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA [3] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
authors.affiliation: 1] Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA [2] Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA [3] Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA [4] Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA [5] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D024201:Bystander Effect / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D015870:Gene Expression; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D036104:Receptor, EphA2 / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000235:genetics; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D017252:CD3 Complex; D036104:Receptor, EphA2