Comparative Evaluation of Synthetic Cytokines for Enhancing Production and Performance of NK92 Cell-Based Therapies.
Journal
GEN biotechnology
ISSN: 2768-1556
Titre abrégé: GEN Biotechnol
Pays: United States
ID NLM: 9918400388506676
Informations de publication
Date de publication:
01 Jun 2023
01 Jun 2023
Historique:
received:
11
05
2023
accepted:
29
05
2023
pmc-release:
22
06
2024
medline:
26
6
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
Off-the shelf immune cell therapies are potentially curative and may offer cost and manufacturing advantages over autologous products, but further development is needed. The NK92 cell line has a natural killer-like phenotype, has efficacy in cancer clinical trials, and is safe after irradiation. However, NK92 cells lose activity post-injection, limiting efficacy. This may be addressed by engineering NK92 cells to express stimulatory factors, and comparative analysis is needed. Thus, we systematically explored the expression of synthetic cytokines for enhancing NK92 cell production and performance. All synthetic cytokines evaluated (membrane-bound IL2 and IL15, and engineered versions of Neoleukin-2/15, IL15, IL12, and decoy resistant IL18) enhanced NK92 cell cytotoxicity. Engineered cells were preferentially expanded by expressing membrane-bound but not soluble synthetic cytokines, without compromising the radiosensitivity required for safety. Some membrane-bound cytokines conferred cell-contact independent paracrine activity, partly attributable to extracellular vesicles. Finally, we characterized interactions within consortia of differently engineered NK92 cells.
Identifiants
pubmed: 37363412
doi: 10.1089/genbio.2023.0024
pii: 10.1089/genbio.2023.0024
pmc: PMC10286265
doi:
Types de publication
Journal Article
Langues
eng
Pagination
228-246Informations de copyright
Copyright 2023, Mary Ann Liebert, Inc., publishers.
Déclaration de conflit d'intérêts
No competing financial interests exist.
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