Abstract 892: Development of iPSC-derived feeder cells to enhance NK cell expansion and cytotoxicity for cancer therapy

Natural killer (NK) cells have been considered a promising candidate for cell therapy in cancer treatment. However, since NK cells constitute a minor fraction of peripheral blood mononuclear cells (PBMCs), recent efforts have concentrated on enhancing the efficiency of in vitro expansion. Among various approaches, the genetically engineered K562 cell line has shown promising potential in NK cell expansion. Nonetheless, as K562 cells are a cell line derived from human leukemia cells, the use of K562 as feeder cells raises significant safety concerns. To address this issue, we developed a novel feeder cell system by engineering hematopoietic progenitor cells (HPCs), derived from induced pluripotent stem cells (iPSCs), to express co-stimulatory molecules and cytokines on their surface via viral transduction. We showed that iPSC-derived HPCs efficiently prolong the lifespan of primary NK cells beyond two weeks, surpassing the typical half-life of NK cells in regular culture conditions. To further enhance the stimulatory effect of membrane-bound interleukin on the surface of feeder cells, we engineered a bispecific antibody comprising a recombinant cytokine and a single-chain variable fragment (scFv) with binding specificity to feeder cells. Interestingly, we found that the combination of HPC feeder cells and recombinant cytokines significantly enhance NK cell expansion and cytotoxicity. We also found that iPSC-derived feeder cells efficiently sustain the cytotoxicity activity of iPSC-derived NK cells, showing that iPSC-derived cells can serve as a powerful platform for cancer therapy. In conclusion, our novel feeder cell system shows great potential to enhance NK cell proliferation and activation. While further optimization is required, this non-cancerous source of feeder cells offers an appealing alternative to K562 cells, facilitating the development of NK cell-based cancer therapy. Citation Format: Zhi-Qian Lin, Meng-Ting Hsu, Yang Lin, Li-Fung Chen, Bing-Hong Chen, Yi-Chen Sun, Kai-Feng Hung. Development of iPSC-derived feeder cells to enhance NK cell expansion and cytotoxicity for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 892.