Promoting the Recruitment, Engagement, and Reinvigoration of Effector T Cells via an Injectable Hydrogel with a Supramolecular Binding Capability for Cancer Immunotherapy

Abstract

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

Engineered cyclodextrin-based supramolecular hydrogels for biomedical applications

“…7D). 180 It was demonstrated that following the recruitment of CCR9 + CD8 + T cells by the chemokine CCL25 released from the hydrogel, the engagement of CD8 + T cells with tumor cells was further facilitated by the anti-PDL1 antibody and anti-PD1 antibody immobilized in the hydrogel via CD/Ad host–guest interactions. Meanwhile, CD8 + T cells were rejuvenated to avoid depletion, ultimately achieving enhanced T cell-mediated immunotherapy efficacy.…”

Shape Self-Adaptive Liquid Embolic Agent for Ultrafast and Durable Vascular Embolization

“…Recently, hydrogels have attracted great attention in biomedical applications including drug delivery, tissue engineering field, etc. − In addition, hydrogels have an abundant selection of components and designable structures to obtain desirable properties such as strong tissue adhesion and injectability. , Unfortunately, hydrogels usually undergo excessive swelling under the wet blood flowing condition of arteries to cause a poor vessel-adhesive performance, which increases the risk of recanalization and even second bleeding injury. , Besides, the mechanical properties of hydrogels are commonly contradictory to their injectability and adhesive capacity, which are essential for vascular embolization . Furthermore, the after-loading of drugs is difficult for prefabricated hydrogel-based embolic agents in clinics, which would further limit their application in the embolization field.…”

Hydrophobization of Ribonucleic Acids for Facile Systemic Delivery and Multifaceted Cancer Immunotherapy

“…To evaluate the transfection efficacy of MNP siRNA , the tumor cell surface receptor CD47, which can reactivate macrophages to recognize and phagocytize tumor cells after down-regulation, − and PD-L1, which may enhance T cell-mediated antitumor immune response when reduced, − were used as target genes. First, after incubation with MNP siCD47 at various concentrations, the CD47 expression in treated B16F10 cells was evaluated.…”