Engineered elastin-like polypeptide-based hydrogel delivering chemotherapeutics and PD-L1 antibodies for potentiated cancer immunotherapy

J Mater Chem B. 2023 Nov 8;11(43):10355-10361. doi: 10.1039/d3tb01974h.

Abstract

Immune checkpoint inhibitors (ICIs) have effectively eradicated advanced tumors by inducing durable and systematic antitumor immune responses. However, when used as a standalone treatment, ICIs typically exhibit a low response rate in many cancers. In this study, we engineered an in situ-formed gel depot using elastin-like polypeptides (ELPs) to efficiently deliver PD-L1 antibodies (aPD-L1) and gemcitabine (GEM) for enhanced immunotherapy in melanoma. Sustainably released chemotherapeutics from gel depots could kill melanoma cells and promote PD-L1 upregulation in tumor cells. Moreover, aPD-L1/GEM-encapsulated ELP hydrogel promoted a 3.0-fold increase of tumor-infiltrated CD8+ T cells and 60% Tregs depletion compared with PBS group, eliciting a robust antitumor immune response for immunotherapy in melanoma mouse models. This research highlights the promising potential of ELP-based hydrogels in delivering ICIs and chemotherapeutic agents for potentiated cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen
  • CD8-Positive T-Lymphocytes*
  • Elastin / therapeutic use
  • Hydrogels / therapeutic use
  • Immunotherapy
  • Melanoma* / drug therapy
  • Mice

Substances

  • B7-H1 Antigen
  • Hydrogels
  • Elastin
  • Antibodies, Monoclonal