title: CD123 redirected multiple virus-specific T cells for acute myeloid leukemia.
abstract: Hematopoietic stem cell transplantation (HSCT) has been increasingly used as a curative treatment for acute myeloid leukemia (AML). However, relapse rates after HSCT in complete remission (CR) are reported between 30% and 70%. In addition, numerous studies suggested that secondary viral infection from a variety of viruses including Epstein-Barr virus (EBV), adenovirus (Adv), and cytomegalovirus (CMV) are among the most common causes of death post-HSCT. Currently, chimeric antigen receptor (CAR)-based T cells have been developed to treat AML in clinical studies, while virus-specific cytotoxic T cells (VST) have been proven to be able to effectively prevent or treat viral infection after HSCT. Thus it would be desirable to develop T cells with the ability of simultaneously targeting AML relapse and viral infection. In this article, we now describe the generation of VST cells that are engineered to express CAR for a specific AML cell-surface antigen CD123 (CD123-CAR-VST). Using Dendritic cells (DCs) pulsed with EBV, Adv, and CMV peptides as sources of viral antigens, we generated VST from A2 donor peripheral mononuclear cells (PBMC). VST were then transduced with retroviral vector encoding CD123-CAR to generate CD123-CAR-VST. We demonstrated that CD123-CAR-VST recognized EBV, Adv, and CMV epitopes and had HLA-restricted virus-specific cytotoxic effector function against EBV target. In addition, CD123-CAR-VST retained the specificity against CD123-positive AML cell lines such as MOLM13 and THP-1 in vitro. Thus our results suggested that CD123-CAR-VST might be a valuable candidate to simultaneously prevent or treat relapse and viral infection in AML HSCT recipients.
authors.affiliation: Shangdong University, Jinan, Shandong, PR China; Department of Hematology, Anhui Provincial Hospital, Hefei, Anhui, PR China; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Hefei, Anhui, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hematology, Anhui Provincial Hospital, Hefei, Anhui, PR China.
authors.forename: Xingbing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shangdong University, Jinan, Shandong, PR China; Department of Hematology, Anhui Provincial Hospital, Hefei, Anhui, PR China. Electronic address: zmsun_vip@163.com.
authors.forename: Zimin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA. Electronic address: xsong1@bcm.edu.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology*; D000998:Antiviral Agents / Q000276:immunology*; D002469:Cell Separation; D058501:Enzyme-Linked Immunospot Assay; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D053650:Interleukin-3 Receptor alpha Subunit / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; D000998:Antiviral Agents; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Acute myeloid leukemia; CD123; Chimeric antigen receptor; Virus-specific cytotoxic T cells