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Beta-2 microglobulin knockout K562 cell-based artificial antigen presenting cells for ex vivo expansion of T lymphocytes.
- Source :
-
Immunotherapy [Immunotherapy] 2019 Aug; Vol. 11 (11), pp. 967-982. Date of Electronic Publication: 2019 Jun 20. - Publication Year :
- 2019
-
Abstract
- Aim: The human K562 leukemia cell line as a scaffold of artificial antigen presenting cells (aAPCs) for ex vivo lymphocyte expansion does not usually express major histocompatibility complex (MHC) molecules. However, when stimulated by supernatants from human T lymphocyte cultures, K562 cells upregulate β-2 microglobulin (B2M) and MHC class I expression, which would induce allo-specific T cells. Methods: We disrupted the B2M locus in K562 cells by CRISPR/Cas9 and achieved MHC class I-negative K562 cells. Results: We further generated K562-based MHC class I-negative aAPC line by zinc-finger nuclease mediated insertion of costimulatory molecules into the AAVS1 locus. This aAPC line could attenuate allogeneic immune responses but support robust antigen-independent and CD19 antigen-specific chimeric antigen receptor-T cell expansion in vitro . Conclusion: B2M-knockout K562 cells provide a new scaffold for aAPC construction and broader application in adoptive immunotherapies.
- Subjects :
- Adoptive Transfer
Antigen-Presenting Cells cytology
Antigens, CD19 genetics
Antigens, CD19 immunology
CRISPR-Cas Systems
Humans
K562 Cells
T-Lymphocytes, Cytotoxic cytology
beta 2-Microglobulin immunology
Antigen-Presenting Cells immunology
Cell Culture Techniques
Cell Proliferation
Gene Knockout Techniques
T-Lymphocytes, Cytotoxic immunology
beta 2-Microglobulin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1750-7448
- Volume :
- 11
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 31218907
- Full Text :
- https://doi.org/10.2217/imt-2018-0211