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Use of Engineered Exosomes Expressing HLA and Costimulatory Molecules to Generate Antigen-specific CD8+ T Cells for Adoptive Cell Therapy.
- Source :
-
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2017 Apr; Vol. 40 (3), pp. 83-93. - Publication Year :
- 2017
-
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.
- Subjects :
- 4-1BB Ligand genetics
4-1BB Ligand metabolism
Antigens, CD genetics
Antigens, CD metabolism
B7-1 Antigen genetics
B7-1 Antigen metabolism
CD8-Positive T-Lymphocytes transplantation
Cross-Priming
Dendritic Cells pathology
Exosomes genetics
Exosomes pathology
Genetic Engineering
HLA-A2 Antigen genetics
HLA-A2 Antigen metabolism
Humans
Immunoglobulins genetics
Immunoglobulins metabolism
K562 Cells
Lymphocyte Activation
MART-1 Antigen immunology
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Neoplasms immunology
Phosphoproteins immunology
Viral Matrix Proteins immunology
Virus Diseases immunology
CD83 Antigen
CD8-Positive T-Lymphocytes immunology
Exosomes metabolism
Immunotherapy, Adoptive methods
Neoplasms therapy
Virus Diseases therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1537-4513
- Volume :
- 40
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy (Hagerstown, Md. : 1997)
- Publication Type :
- Academic Journal
- Accession number :
- 28099196
- Full Text :
- https://doi.org/10.1097/CJI.0000000000000151