title: Use of Engineered Exosomes Expressing HLA and Costimulatory Molecules to Generate Antigen-specific CD8+ T Cells for Adoptive Cell Therapy.
abstract: Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells. Notably, CoEX-A2s also generated similar levels of HCMV pp65-specific and MART1-specific CD8 T cells as DEX in vitro. The results suggest that these novel exosomes may provide a crucial reagent for generating antigen-specific CD8 T cells for adoptive cell therapies against viral infection and tumors.
authors.affiliation: *Catholic Hematopoietic Stem Cell Bank ‡Cancer Research Institute †Departments of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sueon
authors.initials: S
authors.lastname: Kim
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Sohn
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Sohn
authors.forename: Seung-Joo
authors.initials: SJ
authors.lastname: Hyun
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Cho
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D053330:4-1BB Ligand / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045142:Cross-Priming; D003713:Dendritic Cells / Q000473:pathology; D055354:Exosomes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005818:Genetic Engineering; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020014:K562 Cells; D008213:Lymphocyte Activation; D058965:MART-1 Antigen / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010750:Phosphoproteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology / Q000628:therapy*; D000097802:CD83 Antigen
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D018122:B7-1 Antigen; D015789:HLA-A2 Antigen; D007136:Immunoglobulins; D058965:MART-1 Antigen; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D000097802:CD83 Antigen; C065418:cytomegalovirus matrix protein 65kDa