Chimeric antigen receptor NK-92 cell function is modulated by HLA class I expression of target cells

• DOI: 10.1016/j.isci.2025.112523
• Publication Date: 2025-04-23T23:34:07Z
• Authors: Nicolai Stransky; Ranran Ji; Lukas Prause; Katrin Ganser; Winfried S. Wels; Peter Ruth; Stephan M. Huber; Franziska Eckert

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 lower risk of graft-versus-host disease. Here, we evaluated two CAR-NK-92 cell lines, targeting either CD276 or HER2, their potential on-target/off-tumor effects in vitro. CD276-directed showed little dependence on target density, while HER2-directed displayed pronounced mostly sparing with low amounts HER2. The activity both lines was modulated by the expression HLA-I ultimately reducing against cells. Lower modulation can be explained surface inhibitory NK receptors, such as NKG2A ILT-2. These results underscore importance thoroughly testing products fine-tune anti-cancer activity, limiting toxicity.