Charge-altering releasable transporters enable phenotypic manipulation of natural killer cells for cancer immunotherapy.
| Autor: | Wilk AJ; Division of Infectious Diseases and Geographic Medicine, Department of Medicine.; Program in Immunology.; Medical Scientist Training Program., Weidenbacher NL; Department of Chemistry., Vergara R; Division of Infectious Diseases and Geographic Medicine, Department of Medicine., Haabeth OAW; Division of Oncology, Department of Medicine., Levy R; Division of Oncology, Department of Medicine., Waymouth RM; Department of Chemistry., Wender PA; Department of Chemistry.; Department of Chemical and Systems Biology, Stanford University, Stanford, CA; and., Blish CA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine.; Chan Zuckerberg Biohub, San Francisco, CA. |
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| Jazyk: | angličtina |
| Zdroj: | Blood advances [Blood Adv] 2020 Sep 08; Vol. 4 (17), pp. 4244-4255. |
| DOI: | 10.1182/bloodadvances.2020002355 |
| Abstrakt: | Chimeric antigen receptor (CAR) natural killer (NK) cells are an emerging cell therapy with promising results in oncology trials. However, primary human NK cells are difficult to transfect, hampering both mechanistic studies and clinical applications of NK cells. Currently, NK cell CAR modification relies on viral vectors or cell activation. The former raises cost and tolerability issues, while the latter alters NK cell biology. Here, we report that readily synthesized and inexpensive nonviral charge-altering releasable transporters (CARTs) efficiently transfect primary human NK cells with messenger RNA without relying on NK cell activation. Compared with electroporation, CARTs transfect NK cells more efficiently, better preserve cell viability, and cause minimal reconfiguration of NK cell phenotype and function. We use CARTs to generate cytotoxic primary anti-CD19 CAR NK cells, demonstrating this technology can drive clinical applications of NK cells. To our knowledge, CARTs represent the first efficacious transfection technique for resting primary human NK cells that preserves NK cell phenotype and can enable new biological discoveries and therapeutic applications of this understudied lymphocyte subset. (© 2020 by The American Society of Hematology.) |
| Databáze: | MEDLINE |
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