Generation of non-genetically modified, CAR-like, NK cells

非转基因 CAR 样 NK 细胞的产生

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作者:Loïs Coënon, Emilie Rigal #, Hortense Courot #, Caroline Multrier, Sara Zemiti, Jennifer Lambour, Martine Pugnière, Marion de Toledo, Guillaume Bossis, Guillaume Cartron, Bruno Robert, Pierre Martineau, Bénédicte Fauvel, Jessy Presumey, Martin Villalba

Background

Natural killer (NK) cell therapy is considered an attractive and safe strategy for anticancer therapy. Nevertheless, when autologous or allogenic NK cells are used alone, the clinical benefit has been disappointing. This is partially due to the lack of target specificity. Recently, CD19-specific chimeric antigen receptor (CAR)-NK cells have proven to be safe and potent in patients with B-cell tumors. However, the generation of CAR-NK cells is a complicated manufacturing process. We

Conclusions

The Pin technology provides an off-the-shelf NK cell therapy platform to generate CAR-like NK cells, without genetic modifications, that easily target multiple tumor antigens.

Results

CD16a/Pin-mAb interaction is stable for several days and Pin-mAb eNK inherit the mAb specificity and exclusively induce ADCC against targets expressing the cognate antigen. Hence, Pin-mAbs confer long-term selectivity to eNK, which allows specific elimination of the target cells in several in vivo mouse models. Finally, we showed that it is possible to arm eNK with at least two Pin-mAbs simultaneously, to increase efficacy against heterogenous cancer cell populations. Conclusions: The Pin technology provides an off-the-shelf NK cell therapy platform to generate CAR-like NK cells, without genetic modifications, that easily target multiple tumor antigens.

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