Parallel processing of T cells and natural killer cells to enhance in vivo CAR T cell activity against blood and solid cancers
- Author(s)
- Dobson, LJ; Marron, PW; Drabble, AH; Liyanage, TD; Pe, KC; Slaney, CY; Hock, BD; McLellan, AD;
- Details
- Publication Year 2026,Volume 15,Issue #9,Page e70120
- Journal Title
- Clinical & Translational Immunology
- Publication Type
- Research article
- Abstract
- OBJECTIVES: Despite their anti-cancer properties, natural killer (NK) cells are discarded during CAR T cell manufacturing. NK cells display promising responses as a cell therapy, exhibiting remarkable safety at high doses. Moreover, NK cells have complementary cytokine profiles and distinct antigen-recognition pathways to supplement CAR T cell therapies. We demonstrate parallel expansion of NK cells from the normally discarded PBMC of CAR T cell production for downstream combination therapies against solid and blood-borne malignancies. METHODS: CAR T cells were manufactured from buffy coats with initial isolation of T cells from PBMC. NK cells were rapidly expanded in parallel by stimulating the remaining PBMC with membrane-bound (mb)IL-21 + mbIL-15 feeder cells. Expanded NK cells were assessed through spectral flow cytometry and applied as a pretreatment prior to CAR Tcell infusion against xenograft tumor models in NOD-scid IL2Rgamma(null) (NSG) mice. RESULTS: Applying feeder cells to residual PBMC stimulated 5000-fold expansions of pure NK cells. Expanded NK cells expressed various activation receptors and displayed strong in vitro cytotoxicity, which was further improved in CAR T-conditioned medium. A pretreatment of NK cells enhanced existing CAR T cell therapies, improving in vivo tumor clearance and survival against breast cancer, acute lymphoblastic leukaemia and non-Hodgkin's lymphoma. While NK cells eliminated CD19(-/-) variants in vitro, they were unable to suppress antigen-escape relapse in vivo. CONCLUSION: This study encourages the optimal use of leukapheresis product. By recycling discarded PBMC into NK cells, CAR T cell therapies can be effectively enhanced, improving tumor clearance and survival.
- Publisher
- Wiley
- Keywords
- T cell; cell therapy; chimeric antigen receptor; manufacturing; natural killer
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1002/cti2.70120
- Open Access at Publisher's Site
https://doi.org/10.1002/cti2.70120- Terms of Use/Rights Notice
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Creation Date: 2026-10-28 06:10:07
Last Modified: 2026-10-28 06:10:23