Challenges and opportunities on achieving an adequate delivery efficiency and immunogenicity with peptide-based anticancer vaccines.

Peptide vaccines are based on small peptide segments that contain antigenic epitopes recognizable by immune cells. Unlike traditional vaccines, they include only specific antigenic epitopes rather than entire pathogens or proteins. They are recognized, internalized, processed, and presented by antigen-presenting cells, such as dendritic cells, and subsequently presented to T cells, triggering an immune response. Peptide-based vaccines, an innovative regimen of cancer immunotherapy, have shown the potential to elicit target-specific anti-tumor immune responses, however their therapeutic efficacy is often diminished by their poor stability, rapid clearance from circulation, low immunogenicity, individual variability, and immune escape. In recent years, significant advancements have been achieved in the mechanism of action, design, and delivery of potent peptide-based cancer vaccines to address their limitations for clinical translation. Long peptide vaccines are more likely to induce antigen cross-presentation than short peptide vaccines. Tumor-specific peptide antigens and tumor-associated antigens have been developed to enhance anti-cancer immunogenicity. Incorporation of various delivery systems, such as lipid nanoparticles, polymers, and viral vectors substantially improve the stability of peptide antigens in circulation. Co-delivery of the peptide antigens and adjuvants further enhances with antigen presentation and T-cell activation, resulting in robust immunogenicity and efficacious cancer immunotherapy. Combination therapy of peptide vaccines and other therapies, including chemotherapy, radiotherapy, immune checkpoint inhibitors, and targeted therapy also enhances therapeutic outcomes. This article provides insights in cancer peptide vaccines, including the mechanism of action of peptide antigens and adjuvants, while discussing their challenges and opportunities, and exploring the use of delivery systems to improve their pharmacokinetics and therapeutic efficacies for cancer immunotherapy.