Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy

Feihu Wang, Dongqing Xu, Hao Su, Weijie Zhang, Xuanrong Sun, Maya K. Monroe, Rami W. Chakroun, Zongyuan Wang, Wenbing Dai, Richard Oh, Han Wang, Qin Fan, Fengyi Wan, Honggang Cui

Research output: Contribution to journalArticle

Abstract

Immune checkpoint blockers (ICBs) have shown great promise at harnessing immune system to combat cancer. However, only a fraction of patients can directly benefit from the anti-programmed cell death protein 1 (aPD1) therapy, and the treatment often leads to immune-related adverse effects. In this context, we developed a prodrug hydrogelator for local delivery of ICBs to boost the host's immune system against tumor. We found that this carrier-free therapeutic system can serve as a reservoir for extended tumoral release of camptothecin and aPD1 antibody, resulting in an immune-stimulating tumor microenvironment for boosted PD-1 blockade immune response. Our in vivo results revealed that this combination chemoimmunotherapy elicits robust and durable systemic anticancer immunity, inducing tumor regression and inhibiting tumor recurrence and metastasis. This work sheds important light into the use of small-molecule prodrugs as both chemotherapeutic and carrier to awaken and enhance antitumor immune system for improved ICBs therapy.

Original languageEnglish (US)
Article numbereaaz8985
JournalScience Advances
Volume6
Issue number18
DOIs
StatePublished - Apr 2020

ASJC Scopus subject areas

  • General

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    Wang, F., Xu, D., Su, H., Zhang, W., Sun, X., Monroe, M. K., Chakroun, R. W., Wang, Z., Dai, W., Oh, R., Wang, H., Fan, Q., Wan, F., & Cui, H. (2020). Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy. Science Advances, 6(18), [eaaz8985]. https://doi.org/10.1126/sciadv.aaz8985