Delivery of NK cells in an injectable dynamic hydrogel effectively remodels tumor microenvironment and inhibits post-surgery tumor recurrence

Adoptive immunotherapy against cancer based on natural killer (NK) cells has emerged as a promising strategy. However, the efficacy of NK cells in solid tumors is still unsatisfactory, where a major cause is the immune suppressive tumor microenvironment (TME) and limited delivery. Here, an injectable dynamic Schiff’s base hydrogel named SNgel was developed for growth and controlled delivery of NK cells to enhance the treatment of solid tumors. The hydrogel contains interleukin-15 and SCH-442416 nanoparticles coated with MnO 2 along with NK cells. After application, SNgel functions as a reservoir to continuously release NK cells and drugs, thereby improving the distribution and persistence of NK cells in vivo . Simultaneously‌, the platform can enhance the anti-tumor activity of NK cells by alleviating tumor hypoxia and blocking adenosine A2A receptors. As a result, SNgel effectively inhibited post-surgery recurrence of non-small cell lung cancer (NSCLC) with good safety profile. Thus, SNgel has good potential for further development and offers ground for designing other live cell-containing gel.