Intratumoral Injectable Redox‐Responsive Immune Niche Improves the Abscopal Effect in Radiotherapy
Year: 2024
Type: article
Abstract: Radiotherapy (XRT) is often utilized to improve the immune checkpoint blockade response in cancer management. Such combination treatment can enhance the abscopal effect, facilitating a prolonged and durable systemic response. However, despite intense research efforts, only a minority of patients respond to this approach, and novel strategies to increase the abscopal effect are urgently needed. Here, the development of an intratumoral (i.t.) injectable nanofiber (NF)‐based tumor immune niche (TIN) that converts XRT‐treated tumors into an in situ cancer vaccine, eliciting robust systemic antitumor immunity, is reported. This NF‐based immune niche incorporates redox‐degradable anti‐CTLA‐4 (α‐CTLA‐4) nanogels (NGs) and interleukin‐2 (IL‐2) NGs for controlled release in hypoxic irradiated tumors, reversing the immunosuppressive tumor microenvironment into a pro‐inflammatory microenvironment, and expanding the tumor‐infiltrating CD8+ T cell population. Additionally, it is functionalized with polyinosinic‐polycytidylic acid (poly(I:C)) to promote antigen‐presenting cell maturation and prime neoantigen‐specific CD8+ T cells. In vitro studies demonstrate TIN's ability to prime antigen‐specific CD8+ T cells and increase antigen‐specific cell‐killing efficiency under in vitro immunosuppressive conditions. In vivo studies confirm TIN's ability to elicit robust systemic anticancer activity in mouse melanoma and colorectal cancer models without inducing severe immune‐related adverse events.
Source: Advanced Materials
Authors: Kin Man Au, J. Steven Swinnea, Andrew Z. Wang
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, University of Texas Southwestern Medical Center, University of Texas at Austin, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: G1226235601, Basement Membrane Targeted Nanoparticles for Post-Surgical Adhesion Prevention, G2369565188, G3485118910, G3928993440, TEM for UT Southwestern Electron Microscopy Core Facility, Targeting through Selective Cell Labeling, MRI: Acquisition of a Small Angle X-ray Scattering Instrument with In Situ Capabilities, G9000175872, UT Southwestern Medical Center Simmons Comprehensive Cancer Center
OpenAlex ID: W4404114962