Therapeutic supramolecular tubustecan hydrogel combined with checkpoint inhibitor elicits immunity to combat cancer

Feihu Wang, Hao Su, Dongqing Xu, Maya K. Monroe, Caleb F. Anderson, Weijie Zhang, Richard Oh, Zongyuan Wang, Xuanrong Sun, Han Wang, Fengyi Wan, Honggang Cui

Research output: Contribution to journalArticlepeer-review

Abstract

The clinical benefit of PD-1/PD-L1 blockade immunotherapy is substantially restricted by insufficient infiltration of T lymphocytes into tumors and compromised therapeutic effects due to immune-related adverse events following systemic administration. Some chemotherapeutic agents have been reported to trigger tumor-associated T cell responses, providing a promising strategy to achieve potent immune activation in a synergistic manner with PD-1 blockade immunotherapy. In light of this, a localized chemoimmunotherapy system was developed using an anti-cancer drug-based supramolecular polymer (SP) hydrogel to “re-edit” the host's immune system to combat cancer. This in situ forming injectable aPD1/TT6 SP hydrogel serves as a drug-delivery depot for sustained release of bioactive camptothecin (CPT) and aPD1 into the tumor microenvironment, priming the tumor for robust infiltration of tumor-associated T cells and subsequently prompting a response to the immune checkpoint blockade. Our in vivo results demonstrate that this chemoimmunotherapy hydrogel provokes a long-term and systemic anticancer T cell immune response, which elicits tumor regression while also inhibiting tumor recurrence and potential metastasis.

Original languageEnglish (US)
Article number121182
JournalBiomaterials
Volume279
DOIs
StatePublished - Dec 2021

Keywords

  • Chemoimmunotherapy
  • Immune checkpoint blockade
  • Self-supporting hydrogel
  • Supramolecular polymer
  • Sustained release

ASJC Scopus subject areas

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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