ArticleJournal of nanobiotechnology2026
Engineered nanovesicles as a DC vaccine to enhance the antitumor efficacy of CAR-T cells against solid tumors.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDespite the success of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, its efficacy against solid tumors like non-small cell lung cancer (NSCLC) remains limited due to the immunosuppressive tumor microenvironment (TME) and insufficient T-cell infiltration. Dendritic cell (DC) vaccines offer potential to remodel the TME but face challenges with targeted antigen delivery. Therefore, we want to develop a DC-targeted nanovesicle (NV) vaccine to enhance the antitumor activity of CAR-T cells against lung cancer.
resultsWe engineered CD205-targeted nanovesicles (aCD205 NVs) derived from LLC cells displaying anti-CD205 single-chain variable fragments. These NVs were evaluated for DC targeting, maturation induction, and T cell priming in vitro and were injected intravenously with Poly(I: C) as a DC vaccine to reprogram the TME in vivo. The combinatorial effect with mesothelin (MSLN)-targeted CAR-T cells (CAR-T + Vac therapy) was assessed in subcutaneous and orthotopic murine LLC models. We found that CAR-T + Vac therapy significantly enhanced tumor infiltration of CAR-T cells and endogenous T cells, substantially elevated cytotoxic molecules (Granzyme B and Perforin), and pro-inflammatory cytokines (IFN-γ and TNF-α), while reducing immunosuppressive cell populations (M2 macrophages, MDSCs, and Tregs) and IL-10. This synergistic remodeling resulted in potent tumor suppression and markedly prolonged overall survival, with no observable short-term toxicity.
conclusionsThis study establishes a novel combinatorial strategy utilizing CD205-targeted, tumor cell-derived NVs as a DC vaccine to effectively reprogram the immunosuppressive TME. CAR-T + Vac therapy significantly enhances CAR-T cell infiltration and antitumor efficacy against lung cancer, providing a versatile and promising platform for advancing solid tumor immunotherapy.
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