Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy
Deyan Jiao, Min Hao, Renhui Sun, Xiaolei Ren, Yanfei Wei, Miaomiao Ding, Xuetian Yue, Zhuanchang Wu, Chunyang Li, Lifen Gao, Chunhong Ma, Yuanhua Sang, Xiaohong Liang, Hong Liu
Abstract
Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory. Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4–1BB and cytokines IL-2 and IL-21 support survival and dynamic activation. Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.