PBMC-derive eNK cells was armed and promoted CAR-like response against tumors through armed with 16Fc21, a novel bispecific fusion protein for NK cells.

INTRODUCTION: Cell-based immunotherapies of PBMC-derive Natural killer (NK) cells have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the complex and inefficient gene modification in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. METHODS: Herein, a novel bispecific fusion protein 16Fc21(Anti-CD16A-FC-IL21) with capacity of modulate NK cell function is designed and constructed to try to breakthrough these limitations. RESULTS: In this work, we demonstrated that 16Fc21 has excellent ability to induce the functional activation of PBMC-derived NK cells and improve the therapeutic efficacy of NK cell immunotherapy for solid tumors in vivo. Additionally, we developed a novel combination therapy by combining adoptive transfer of NK cell with 16Fc21. We pre-arming 16Fc21 onto the surface of NK cells and successfully developed a non-genetically modified 16Fc21 armedNK (16Fc21 armed-eNK) technology platform. DISCUSSION: We confirmed that this novel combination therapy can effectively improve the survival and proliferation of NK cells in vivo, offering a safer and more effective way to enhance their therapeutic effects in vivo. This approach provides a solution to the challenges of the cumbersome in vitro gene modification of PBMC-derived NK cells and their insufficient therapeutic in vivo.