Rational Design of Hyaluronic Acid-Based Copolymer-Mixed Micelle in Combination PD-L1 Immune Checkpoint Blockade for Enhanced Chemo-Immunotherapy of Melanoma

Abstract

The application of combinational therapy breaks the limitation of monotherapy and achieves better clinical benefit for tumor therapy. Herein, a hyaluronic acid/Pluronic F68-based copolymer-mixed micelle was constructed for targeted delivery of chemotherapeutical agent docetaxel (PHDM) in combination with programmed cell death ligand-1(PD-L1) antibody. When PHDM+anti-PDL1 was injected into the blood system, PHDM could accumulate into tumor sites and target tumor cells via CD44-mediated endocytosis and possess tumor chemotherapy. While anti-PDL1 could target PD-L1 protein expressed on surface of tumor cells to the immune checkpoint blockade characteristic for tumor immunotherapy. This strategy could not only directly kill tumor cells but also improve CD8+ T cell level and facilitate effector cytokines release. In conclusion, the rational-designed PHDM+anti-PDL1 therapy strategy creates a new way for tumor immune-chemotherapy.

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

“…Checkpoint blockade immunotherapy has emerged as a promising direction in the clinical treatment of CM ( Huang and Zappasodi, 2022 ). Immune checkpoint inhibitors, such as CTLA-4 , PD-1 , PD-L1 , and PD-L2 , regulated the function and inhibited the antitumor immunity of activated T cells ( Zhou et al, 2021 ). In the current study, the IPS result suggested that low-risk score patients displayed a greater response to the anti- CTLA-4 , anti- PD-1 , and anti- CTLA-4 /anti- PD-1 of CM.…”

Nanomaterials for Drug Delivery and Cancer Therapy

“…IVT-mRNA is inherently immunogenic, it activates pattern recognition receptors (PRRs) such as Toll-like receptors (TLR-3, TLR-7, and TLR-8) in the endosomal compartments of host cells [184,185]. In some cases, activation of innate immunity by IVT-mRNA is potentially advantageous for vaccines, as it promotes recruitment of DCs to the administra-tion site and subsequent maturation of DCs to elicit potent adaptive immunity.…”

“…Moreover, CUR [180] and rosiglitazone (ROZ) [181] were co-loaded as MDR reversing and adipogenesis agents, respectively. HA-SANPs were also obtained with HA-VES and proposed as nanocarriers for DOX treatment in Adriamycin resistant breast cancer cells [182], as well as for the combined DOX/CUR [183] or DTX/programmed cell death ligand 1 (PD-L1) antibodies (anti-PD-L1) [184] protocols exploiting CUR as coadjuvant and the Anti-PD-L1 as an immune checkpoint.…”