Cargando…
Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways
Clinical success of chimeric antigen receptor (CAR) T cell immunotherapy requires the engineering of autologous T cells, which limits the broader implementation of CAR cell therapy. The development of allogeneic and universal cell products will significantly broaden their application and reduce cost...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364029/ https://www.ncbi.nlm.nih.gov/pubmed/32695845 http://dx.doi.org/10.1016/j.omtm.2020.06.014 |
_version_ | 1783559757294993408 |
---|---|
author | Yang, Yan Badeti, Saiaditya Tseng, Hsiang-chi Ma, Minh Tuyet Liu, Ting Jiang, Jie-Gen Liu, Chen Liu, Dongfang |
author_facet | Yang, Yan Badeti, Saiaditya Tseng, Hsiang-chi Ma, Minh Tuyet Liu, Ting Jiang, Jie-Gen Liu, Chen Liu, Dongfang |
author_sort | Yang, Yan |
collection | PubMed |
description | Clinical success of chimeric antigen receptor (CAR) T cell immunotherapy requires the engineering of autologous T cells, which limits the broader implementation of CAR cell therapy. The development of allogeneic and universal cell products will significantly broaden their application and reduce costs. Allogeneic natural killer (NK) cells can be used for universal CAR immunotherapy. Here, we develop an alternative approach for the rapid expansion of primary NK and CAR-NK cells with superior expansion capability and in vivo cytotoxicity from various sources (including peripheral blood, cord blood, and tumor tissue). We apply a human B-lymphoblastoid cell-line 721.221 (hereinafter, 221)-based artificial feeder cell system with membrane-bound interleukin 21 (mIL-21) to propagate NK and CAR-NK cells. The expansion capability, purity, and cytotoxicity of NK cells expanded with 221-mIL-21 feeder cells are superior to that of conventional K562-mIL-21 feeder cells. RNA sequencing (RNA-seq) data show that 221-mIL-21 feeder cell-expanded NK cells display a less differentiated, non-exhausted, limited fratricidal, memory-like phenotype correlated with enriched metabolic pathways, which explains underlying mechanisms. Thus, “off-the-shelf” NK and CAR-NK cells with superior functionalities and expansion using a genetically modified 221-mIL-21 feeder cell expansion system will greatly support clinical use of NK immunotherapy. |
format | Online Article Text |
id | pubmed-7364029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-73640292020-07-20 Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways Yang, Yan Badeti, Saiaditya Tseng, Hsiang-chi Ma, Minh Tuyet Liu, Ting Jiang, Jie-Gen Liu, Chen Liu, Dongfang Mol Ther Methods Clin Dev Article Clinical success of chimeric antigen receptor (CAR) T cell immunotherapy requires the engineering of autologous T cells, which limits the broader implementation of CAR cell therapy. The development of allogeneic and universal cell products will significantly broaden their application and reduce costs. Allogeneic natural killer (NK) cells can be used for universal CAR immunotherapy. Here, we develop an alternative approach for the rapid expansion of primary NK and CAR-NK cells with superior expansion capability and in vivo cytotoxicity from various sources (including peripheral blood, cord blood, and tumor tissue). We apply a human B-lymphoblastoid cell-line 721.221 (hereinafter, 221)-based artificial feeder cell system with membrane-bound interleukin 21 (mIL-21) to propagate NK and CAR-NK cells. The expansion capability, purity, and cytotoxicity of NK cells expanded with 221-mIL-21 feeder cells are superior to that of conventional K562-mIL-21 feeder cells. RNA sequencing (RNA-seq) data show that 221-mIL-21 feeder cell-expanded NK cells display a less differentiated, non-exhausted, limited fratricidal, memory-like phenotype correlated with enriched metabolic pathways, which explains underlying mechanisms. Thus, “off-the-shelf” NK and CAR-NK cells with superior functionalities and expansion using a genetically modified 221-mIL-21 feeder cell expansion system will greatly support clinical use of NK immunotherapy. American Society of Gene & Cell Therapy 2020-06-24 /pmc/articles/PMC7364029/ /pubmed/32695845 http://dx.doi.org/10.1016/j.omtm.2020.06.014 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Yang, Yan Badeti, Saiaditya Tseng, Hsiang-chi Ma, Minh Tuyet Liu, Ting Jiang, Jie-Gen Liu, Chen Liu, Dongfang Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways |
title | Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways |
title_full | Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways |
title_fullStr | Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways |
title_full_unstemmed | Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways |
title_short | Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways |
title_sort | superior expansion and cytotoxicity of human primary nk and car-nk cells from various sources via enriched metabolic pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364029/ https://www.ncbi.nlm.nih.gov/pubmed/32695845 http://dx.doi.org/10.1016/j.omtm.2020.06.014 |
work_keys_str_mv | AT yangyan superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT badetisaiaditya superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT tsenghsiangchi superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT maminhtuyet superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT liuting superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT jiangjiegen superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT liuchen superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways AT liudongfang superiorexpansionandcytotoxicityofhumanprimarynkandcarnkcellsfromvarioussourcesviaenrichedmetabolicpathways |