Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors

扩增同种异体 NK 细胞,对多种肿瘤具有有效的抗体依赖性细胞毒作用

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作者:Diego Sanchez-Martinez, Nerea Allende-Vega, Stefania Orecchioni, Giovanna Talarico, Amelie Cornillon, Dang-Nghiem Vo, Celine Rene, Zhao-Yang Lu, Ewelina Krzywinska, Alberto Anel, Eva M Galvez, Julian Pardo, Bruno Robert, Pierre Martineau, Yosr Hicheri, Francesco Bertolini, Guillaume Cartron, Martin

Conclusion

We have established a new protocol for activation/expansion of NK cells with high ADCC activity. The use of mAbs in combination with e-NK cells could potentially improve cancer treatment.

Methods

We combined allogeneic NK cells and mAbs to improve cancer treatment. We generated expanded NK cells (e-NK) with strong in vitro and in vivo ADCC responses against different tumors and using different therapeutic mAbs, namely rituximab, obinutuzumab, daratumumab, cetuximab and trastuzumab.

Results

Remarkably, e-NK cells can be stored frozen and, after thawing, armed with mAbs. They mediate ADCC through degranulation-dependent and -independent mechanisms. Furthermore, they overcome certain anti-apoptotic mechanisms found in leukemic cells.

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