Promoting The Recruitment, Engagement, And Reinvigoration of Effector T Cells via An Injectable Hydrogel with A Supramolecular Binding Capability for Cancer Immunotherapy.

T cells play a basic and key role in immunotherapy against solid tumors, and efficiently recruiting them into neoplastic foci and sustaining long-term effector function are consistent goals that remain a critical challenge. Here, an injectable alginate-based hydrogel with abundant β-cyclodextrin (ALG-βCD) sites was developed and intratumorally injected to recruit CCR9 + CD8 + T cells (a subset of T cells with robust antitumor activity) via the trapped chemokine CCL25. In the meantime, an intravenously injected adamantane-decorated anti-PD1 antibody (Ad-aPD1) would hitchhike on recruited CCR9 + CD8 + T cells to achieve the improved intratumoral accumulation of Ad-aPD1. Moreover, the Ad-PD1 and Ad-PDL1 antibodies were immobilized in the ALG-βCD hydrogel through supramolecular host-guest interactions of Ad and βCD, which facilitated engagement between CD8 + T cells and tumor cells and reinvigorated CD8 + T cells to avoid exhaustion. Base on this treatment strategy, T cell-mediated anticancer activity was promoted at multiple levels, eventually achieving superior antitumor efficacy in both orthotopic and postsurgical B16-F10 tumor models. This article is protected by copyright. All rights reserved.