A bio-responsive, cargo-catchable gel for postsurgical tumor treatment via ICD-based immunotherapy

Abstract

Tumor recurrence and metastasis after surgery remain challenges for tumor treatment. Strategy that can promote the immunogenicity, activate adaptative immune response and eliminate post-operative immunosuppression would be a promising way to achieve a desired clinical benefit. In this study, immunogenic cell death (ICD) priming anti-tumor adaptive immune response was executed to potentiate immune checkpoint blockade (ICB) therapy through the PD1/PDL1 pathway for postsurgical treatment. Here, we present a bio-responsive and cargo-catchable gel depot composed of pullulan and chitosan cross-linking through matrix metalloproteinase (MMP) sensitive peptide for co-delivery of anti-programmed death-ligand 1 antibody (aPDL1) and doxorubicin -encapsulated liposomes (DOX-Lip). This drug carrier showed expected ability to respond to the highly expressed MMP in postsurgical tumor microenvironment (TME). In vivo studies on 4T1 breast tumor mouse model demonstrated that the gel depot could efficiently prolong the mouse survival after tumor resection by preventing tumor recurrence and metastasis. The results suggested that ICD combining with PD1/PDL1 blockade based on the bio-responsive and cargo-catchable gel depot could facilitate the maturation of DCs and reverse the immunosuppressive environment in tumor resection area, thus amplifying the systemic anti-tumor immune response.

Keywords: Combination immunotherapy; Gel depot; Immunogenic cell death (ICD); PD1/PDL1 blockade; Postsurgical.