Cytotherapy · 2025
Mannan-targeting chimeric antigen receptor redirected antifungal activity of NK-92 cells against Candida albicans.
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de Campos Gabriela Yamazaki, Guimarães Júlia Garcia, Machado Michele Procópio, Oliveira-Brito Patrícia Kellen Martins, Shin Ben, Maio Antonio Di, Dos-Santos Douglas, Palma Patricia Vianna Bonini, Dos Reis Thaila Fernanda, Goldman Gustavo Henrique, Palma Angelina S, Matthews Steve J, Feizi Ten, Liu Yan, da Silva Thiago Aparecido
Аннотация
Chimeric antigen receptors (CARs) offer promising prospects for innovative cell-based therapies against invasive fungal infections such as invasive candidiasis. Here, we have developed 4 CARs targeting Candida albicans with distinct single-chain variable fragments (scFvs): scFv3-CAR, scFv5-CAR, scFv12-CAR, and scFvκ3-1-CAR. In T cells, scFv5-CAR induced IL-2 expression in response to C. albicans hyphae, while scFv3-CAR and scFv12-CAR did not mediate cell activation against C. albicans. Notably, scFvκ3-1-CAR mediated the strongest cell activation against C. albicans yeast, hyphae, and other clinically relevant Candida species. scFvκ3-1-CAR-NK-92 cells exhibited elevated IFN-γ and CD107a expression, reducing C. albicans viability. NOD scid gamma (NSG) mice treated with scFvκ3-1-CAR-NK-92 cells had reduced C. albicans burden in the kidneys 24 hours postinfection. We showed that scFvκ3-1-CAR targets C. albicans mannan but no other glycans in glycan microarray screening analyses. These findings reveal the scFvκ3-1-CAR potential as a therapeutic strategy for treating Candida spp. by modifying peripheral blood mononuclear cells.