美国加州大学洛杉矶分校Lili Yang研究团队取得一项新进展，他们利用造血干细胞工程化的恒定自然杀伤T（iNKT）开发出可用于癌症的细胞疗法。2019年9月5日，《细胞—干细胞》在线发表了这项成果。

研究人员提供了造血干细胞工程化iNKT（HSC-iNKT）细胞疗法的概念性验证，其具有为患者一生提供治疗水平iNKT细胞的潜力。使用人类HSC移植小鼠模型和人类iNKT TCR基因工程方法，研究人员证明了体内HSC-iNKT细胞的有效和长期生成。这些HSC-iNKT细胞与内源性人iNKT细胞非常相似，可以部署多种机制来攻击肿瘤细胞，并在多种人肿瘤异种移植小鼠模型中有效抑制体内肿瘤生长。临床前安全性研究显示HSC-iNKT细胞疗法没有毒性或致瘤性。总之，这些结果证明了所提出的HSC-iNKT细胞疗法的可行性、安全性和癌症治疗潜力，并为将来的临床开发奠定了基础。

据了解，恒定自然杀伤T细胞是靶向癌症的有效免疫细胞；然而，其临床应用因癌症患者中细胞数较少而受到阻碍。

附：英文原文

Title: Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer

Author: Yanni Zhu, Drake J. Smith, Yang Zhou, Yan-Ruide Li, Jiaji Yu, Derek Lee, Yu-Chen Wang, Stefano Di Biase, Xi Wang, Christian Hardoy, Josh Ku, Tasha Tsao, Levina J. Lin, Alexander T. Pham, Heesung Moon, Jami McLaughlin, Donghui Cheng, Roger P. Hollis, Beatriz Campo-Fernandez, Fabrizia Urbinati, Liu Wei, Larry Pang, Valerie Rezek, Beata Berent-Maoz, Mignonette H. Macabali, David Gjertson, Xiaoyan Wang, Zoran Galic, Scott G. Kitchen, Dong Sung An, Siwen Hu-Lieskovan, Paula J. Kaplan-Lefko, Satiro N. De Oliveira, Christopher S. Seet, Sarah M. Larson, Stephen J. Forman, James R. Heath, Jerome A. Zack, Gay M. Crooks, Caius G. Radu, Antoni Ribas, Donald B. Kohn, Owen N. Witte, Lili Yang

Issue&Volume: 5 September 2019

Abstract: Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patients lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.

DOI: 10.1016/j.stem.2019.08.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30339-X