Poly(cyclodextrin)-Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Immunotherapy

Background:

• Oncolytic virus therapy is approved for advanced melanoma but has limitations like infection risk and high manufacturing costs.
• Developing virus-free alternatives that mimic oncolytic virus therapeutic effects is crucial for overcoming these challenges.

Purpose of the Study:

• To develop and evaluate a novel nanoassembly (pTX/pCD-pSNO) as a virus-free alternative to oncolytic virus therapy.
• To investigate the chemo- and immunotherapeutic potential of this nanoassembly for cancer treatment.

Main Methods:

• A nanoassembly was created using polymerized paclitaxel (pPTX) and nitric oxide-incorporated polymerized β-cyclodextrin (pCD-pSNO).
• In vitro studies assessed cytotoxicity, immunogenic cell death, dendritic cell activation, and T cell expansion.
• In vivo studies involved intratumoral administration in animal models, with and without anti-CTLA-4 antibody treatment.

Main Results:

• The pPTX/pCD-pSNO nanoassembly demonstrated enhanced cytotoxicity and immune cell activation in vitro.
• Intratumoral administration induced systemic dendritic cell activation but also myeloid-derived suppressor cells and CD8+ T cell suppression in vivo.
• Combination therapy with anti-CTLA-4 antibody significantly enhanced anti-cancer effects and prolonged survival.

Conclusions:

• The pPTX/pCD-pSNO nanoassembly effectively combines chemotherapy and immunotherapy, mimicking oncolytic virus benefits without viral risks.
• This virus-free nanoformulation presents a promising strategy for advanced melanoma treatment, leveraging synergistic chemo- and immunotherapeutic effects.