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

  • J Mater Chem B. 2023 Oct 11. doi: 10.1039/d3tb01974h.
Jinguang Chen  1 Meiying Cui  2  3 Lianping He  3 Yeteng Mu  3 Nannan Hu  3 Xingang Guan  3
Affiliations
  • 1. Department of Dermatology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou 318001, P. R. China.
  • 2. Department of Clinical Laboratory, Affiliated Hospital of Jining Medical College, Jining 272007, China.
  • 3. Department of Basic Medical Science, Medical School, Taizhou University, Taizhou 318001, P. R. China. [email protected].
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.

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