title: CD123-Engager T Cells as a Novel Immunotherapeutic for Acute Myeloid Leukemia.
abstract: Immunotherapy with CD123-specific T-cell engager proteins or with T cells expressing CD123-specific chimeric antigen receptors is actively being pursued for acute myeloid leukemia. T cells secreting bispecific engager molecules (ENG-T cells) may present a promising alternative to these approaches. To evaluate therapeutic potential, we generated T cells to secrete CD123/CD3-bispecific engager molecules. CD123-ENG T cells recognized primary acute myeloid leukemia (AML) cells and cell lines in an antigen-dependent manner as judged by cytokine production and/or tumor killing, and redirected bystander T cells to AML cells. Infusion of CD123-ENG T cells resulted in regression of AML in xenograft models conferring a significant survival advantage of treated mice in comparison to mice that received control T cells. At high effector to target ratios, CD123-ENG T cells recognized normal hematopoietic stem and progenitor cells (HSPCs) with preferential recognition of HSPCs from cord blood compared to bone marrow. We therefore introduced the CD20 suicide gene that can be targeted in vivo with rituximab into CD123-ENG T cells. The expression of CD20 did not diminish the anti-AML activity of CD123-ENG T cells, but allowed for rituximab-mediated ENG-T cell elimination. Thus, ENG-T cells coexpressing CD20 suicide and CD123 engager molecules may present a promising immunotherapeutic approach for AML.
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 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, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 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, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 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, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nicholos
authors.initials: N
authors.lastname: Joseph
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 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, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Kota
authors.initials: K
authors.lastname: Iwahori
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Amos
authors.initials: A
authors.lastname: Gaikwad
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Phuong
authors.initials: P
authors.lastname: Nguyen
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas, 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, USA.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
authors.affiliation: Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Redell
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.|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; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053650:Interleukin-3 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D012190:Retroviridae / Q000235:genetics; D000069283:Rituximab / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D018951:Antigens, CD20; D017252:CD3 Complex; D016207:Cytokines; D053650:Interleukin-3 Receptor alpha Subunit; D000069283:Rituximab; D003165:Complement System Proteins