Authors
Junfei Zhu, Licheng Bai, Chun Wang, Jiating Liu, Yuhua Chen, Wenxia Zhang, Jun Weng, Lin Wei, Zigong Wei
Published in
Materials today. Bio. Volume 39. Pages 103505. Epub Jul 28, 2026.
Abstract
The clinical efficacy of peptide-based cancer vaccines is limited by inefficient lymphatic delivery and suboptimal antigen presentation. Here, we report a rationally engineered class of lipid-antigen conjugates that co-enhance lymph node (LN) targeting and antigen-presenting cell (APC) uptake through molecular-level structural optimization. By systematically varying lipid tail composition and linker chemistry, we identify a lead construct (dOA-K-O) incorporating a dioleic acid (dOA) lipid tail and an L-lysine (K) linker, which outperforms the clinically used DSPE-PEG2000 conjugate (DSPE-O). Mechanistically, the positively charged L-lysine linker promotes albumin binding while reducing excessive self-assembly, enhancing lymphatic trafficking and facilitating APC internalization. In vivo, dOA-K-O elicits robust antigen cross-presentation and induces an 8-fold increase in antigen-specific CD8+ T cell responses compared to unmodified antigenic peptide and 3-fold higher than DSPE-O. This enhanced cellular immunity translates into marked tumor suppression in both prophylactic and therapeutic B16-OVA melanoma models. Our results establish a design paradigm in which linker chemistry and lipid tail composition are synergistically optimized to boost the immunogenicity of peptide vaccines for cancer immunotherapy, which may provide a chemical and structural basis for the optimization of peptide-based vaccine delivery systems.
PMID:
42571391
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.
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