title: Redirecting T Cell Specificity Using T Cell Receptor Messenger RNA Electroporation.
abstract: Autologous T lymphocytes genetically modified to express T cell receptors or chimeric antigen receptors have shown great promise in the treatment of several cancers, including melanoma and leukemia. In addition to tumor-associated antigens and tumor-specific neoantigens, tumors expressing viral peptides can also be recognized by specific T cells and are attractive targets for cell therapy. Hepatocellular carcinoma cells often have hepatitis B virus DNA integration and can be targeted by hepatitis B virus-specific T cells. Here, we describe a method to engineer hepatitis B virus-specific T cell receptors in primary human T lymphocytes based on electroporation of hepatitis B virus T cell receptor messenger RNA. This method can be extended to a large scale therapeutic T cell production following current good manufacturing practice compliance and is applicable to the redirection of T lymphocytes with T cell receptors of other virus specificities such as Epstein-Barr virus, cytomegalovirus, and chimeric receptors specific for other antigens expressed on cancer cells.
authors.affiliation: Singapore Institute for Clinical Sciences, Brenner Center for Molecular Medicine, Agency for Science, Technology and Research, (A*STAR), 30 Medical Drive, Singapore, Singapore. sarene_koh@sics.a-star.edu.sg.
authors.forename: Sarene
authors.initials: S
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Noriko
authors.initials: N
authors.lastname: Shimasaki
authors.affiliation: Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D018274:Electroporation; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell
keywords: Cell therapy; Electroporation; Hepatitis B virus; Hepatocellular carcinoma; Messenger RNA; T cell receptor; T cells