Immortalized nanodendritic cells decorated with immune-checkpoint inhibitors for personalized cancer immunotherapy

초록

In our study, we have designated artificial nanoDCs (anDCs) by transferring the whole DC membrane onto the gold nanoparticles (Au NPs) to overcome the limitation of DC therapy. The anDCs were optimized by varying membrane-to-substrate ratio, exhibiting similar features with natural DC in having a T cell stimulation and tumor regression even after long-term stability of up to 30 days. This versatile anDCs platform allows engineering immune-boosting agents onto their surface on demand. We further functionalized one of the immune checkpoint inhibitors (ICI), αCTLA-4, on anDCs, leading to complete tumor clearance compared to DC membrane vesicles. Surprisingly, αCTLA-4 conjugated anDC (αCTLA-4-anDC) dramatically blocked the CTLA-4 pathway and resulted in increased frequency and effector cytokine functions in cytotoxic CD8+ T cells. Thus, our anDC system can effectively induce a tumor-specific T cell immune response by sustainable and potent T cell priming ability based on the high stability of anDCs, suggesting a great potential platform for next-generation personalized cancer immunotherapy. © 2024 Elsevier Ltd

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