Multifunctional nano-vaccines integrating lipid-conjugated tumor antigens with TLR/STING agonists enhance cancer immunotherapy.
The paper describes a polymer-based polyvalent peptide and adjuvant platform, SPPA, designed to address limitations of neoantigen peptide vaccines such as poor antigen stability, inefficient delivery, and inadequate immune activation. SPPA co-delivers lipid-conjugated tumor-specific peptides with a TLR7/8 agonist, 3M-052, and a STING agonist, 2'3'-cGAMP, to improve peptide encapsulation, sustained release, and targeted delivery to antigen-presenting cells. In vitro, SPPA upregulated pro-inflammatory genes and cytokine secretion and showed effective cellular uptake and lymphatic trafficking. In vivo, SPPA alone or with anti-PD-1 antibody elicited cytotoxic T lymphocyte responses and inhibited tumor growth in four aggressive syngeneic mouse models, including triple-negative breast cancer.