Qihan Bio and Zhejiang University Co-Develop Next-Generation iPSC-Derived CD70 CAR-NK Cells for Potent Anti-Tumor Activity and Enhanced In Vivo Persistence

Jan 13, 2025 07:21 CST Updated 07:21

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January 13, 2025

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Recently, Zhejiang University has collaborated with Hangzhou Qihan Biotech Co., Ltd. inCell Reports MedicineThe research paper titled "CD70-Targeted iPSC-Derived CAR-NK Cells Display Potent Function Against Tumors and Alloreactive T cells" was published online. Professor He Huang, Professor Yongxian Hu, and Researcher Dongrui Wang from Zhejiang University, along with Dr. Luhuan Yang from Hangzhou Qihan Biotech Co., Ltd., are the corresponding authors. Doctoral students Linqin Wang and Yiyun Wang from Zhejiang University, Xiangjun He from Qihan Biotech, and Postdoctoral Fellow Zhuo Mo from the Liangzhu Laboratory of Zhejiang University are the co-first authors.

NK cells are innate immune cells that can recognize and eliminate abnormal cells. They lack TCR expression, thus posing no risk of inducing graft-versus-host disease when infused between allogeneic individuals, making them a natural universal cell therapy product. However, the multi-gene editing and in vitro expansion efficiency of primary cells remain relatively limited. Therefore, the research team has established a robust production system for iPSC-derived NK cells to achieve batch production. Moreover, iPSC-derived NK cells are amenable to multi-gene editing, enabling the updating and iteration of cellular products, and hold significant clinical application potential.

The weak ability to eliminate tumors and the short survival time in vivo are the current bottlenecks of NK cell therapy. Based on the advantage of iPSC being conducive to multi-gene editing,ResearchThe team introduced various functional components into iPSCs. In terms of anti-tumor capability, the team introduced a CD70-targeting CAR molecule into iPSCs to target pan-cancer and incorporated hnCD16 to enhance the inherent ADCC effect of NK cells. Regarding the persistence and proliferation ability of NK cells, the team introduced CD70 KO in iPSCs to avoid 70CAR-mediated self-killing and incorporated IL15RF to enhance the expansion capability of NK cells.

Furthermore, the research team successfully directed the differentiation of multi-gene edited iPSCs into 70CAR-iNK cells, which can effectively eliminate various solid tumor and hematological tumor cells through the inherent anti-tumor effects of NK cells and the CD70-CAR component. In xenograft mouse tumor models, the research team further confirmed that 70CAR-iNK cells can effectively inhibit the progression of lymphoma and renal cancer in mice. Additionally, the study found that the expression level of CD70 in allogeneic reactive T (alloT) cells induced in vitro gradually increased, and CD70 expression was closely related to the allogeneic reactivity of T cells. 70CAR-iNK cells can eliminate CD70-positive alloT cells, thereby reducing their activity in rejecting NK cells through allogeneic reactions in vivo, thus improving the in vivo persistence of iNK cells.

The study constructed iPSC-derived multi-gene edited CD70 CAR-NK cells and revealed their potent anti-tumor functionality along with the ability to eliminate alloT cells, promoting in vivo persistence, providing crucial evidence for clinical translation.

References:

[1] Qihan Biotech Official WeChat

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