Dibenzocyclooctyne Conjugation Enhances Antigen Cross-Presentation and T-Cell Killing for Potent Cancer Vaccines.

Cancer vaccines have gained considerable attention for tumor prevention and therapy; however, their clinical efficacy remains limited by insufficient activation of antigen-specific cytotoxic T lymphocytes (CTLs). This limitation is primarily due to the inability of conventional vaccine components to effectively promote dendritic-cell-mediated cross-presentation and activation. While adjuvants are often used to enhance this interaction, many conventional adjuvants suffer from poor biocompatibility and systemic toxicity, limiting their clinical utility. Here, we report a vaccine strategy that leverages the bioorthogonal click chemistry reagent dibenzocyclooctyne (DBCO) as an adjuvant-like immune enhancer to promote cross-presentation and a CTL response. DBCO modification to antigen significantly increased antigen uptake by dendritic cells in vitro and promoted MHC class I-mediated cross-presentation via activation of the NF-κB/iNOS signaling pathway. In murine tumor models, systemic administration of DBCO-conjugated protein vaccines elicited enhanced CD8+ T-cell activation, leading to improved tumor control and long-term immune memory. Furthermore, DBCO-modified protein vaccines significantly suppressed tumor metastasis when combined with anti-PD-1 treatment. Collectively, our findings extend the immunotherapeutic potential of click chemistry reagents and establish a promising platform for enhancing CTL-mediated cancer vaccine efficacy in clinical settings.

• Publication year

  2026

• Venue

  Journal of the American Chemical Society

• Publication date

  2026-02-17

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/jacs.5c17189PMID 41701113
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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