2024-04-19 バージニア工科大学(VirginiaTech)
<関連情報>
- https://news.vt.edu/articles/2024/04/researchers-develop-a-new-way-to-safely-boost-immune-cells-to-fi.html
- https://www.science.org/doi/10.1126/sciadv.adk7695
非共有結合で粒子に固定化されたサイトカインが、安全に強力な抗腫瘍免疫を引き起こす Noncovalently particle-anchored cytokines with prolonged tumor retention safely elicit potent antitumor immunity
LIQIAN NIU, EUNGYO JANG, AI LIN CHIN, ZIYU HUO, […], AND RONG TONG
Science Advances Published:19 Apr 2024
DOI:https://doi.org/10.1126/sciadv.adk7695
Abstract
Preclinical studies have shown that immunostimulatory cytokines elicit antitumor immune responses but their clinical use is limited by severe immune-related adverse events upon systemic administration. Here, we report a facile and versatile strategy for noncovalently anchoring potent Fc-fused cytokine molecules to the surface of size-discrete particles decorated with Fc-binding peptide for local administration. Following intratumoral injection, particle-anchored Fc cytokines exhibit size-dependent intratumoral retention. The 1-micrometer particle prolongs intratumoral retention of Fc cytokine for over a week and has minimal systemic exposure, thereby eliciting antitumor immunity while eliminating systemic toxicity caused by circulating cytokines. In addition, the combination of these particle-anchored cytokines with immune checkpoint blockade antibodies safely promotes tumor regression in various syngeneic tumor models and genetically engineered murine tumor models and elicits systemic antitumor immunity against tumor rechallenge. Our formulation strategy renders a safe and tumor-agnostic approach that uncouples cytokines’ immunostimulatory properties from their systemic toxicities for potential clinical application.
