Chimeric antigen receptor NK-92 cell function is modulated by HLA class I expression of target cells
Summary: Chimeric antigen receptors – natural killer (CAR-NK) cells are a promising new cancer treatment approach. They possess distinct benefits over CAR-T cells, including an intrinsic ability to differentiate between malignant and non-malignant cells, and a lower risk of graft-versus-host disease...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225007849 |
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| Summary: | Summary: Chimeric antigen receptors – natural killer (CAR-NK) cells are a promising new cancer treatment approach. They possess distinct benefits over CAR-T cells, including an intrinsic ability to differentiate between malignant and non-malignant cells, and a lower risk of graft-versus-host disease. Here, we evaluated two CAR-NK-92 cell lines, targeting either CD276 or HER2, and their potential on-target/off-tumor effects in vitro. CD276-directed CAR-NK-92 cells showed little dependence on target antigen density, while HER2-directed CAR-NK-92 displayed a pronounced dependence on target antigen density, mostly sparing target cells with low amounts of HER2. The activity of both cell lines was modulated by the expression of HLA-I on target cells, ultimately reducing their activity against non-malignant cells. Lower modulation of activity of HER2-directed CAR-NK-92 can be explained by the lower surface expression of inhibitory NK receptors, such as NKG2A and ILT-2. These results underscore the importance of thoroughly testing new cell products to fine-tune anti-cancer activity, while limiting potential on-target/off-tumor toxicity. |
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| ISSN: | 2589-0042 |