Research Progress in Breast Cancer Vaccination

Breast cancer (BC), a leading global malignancy and cause of cancer death in women which faces limitations with conventional therapies and efficacy of immune checkpoint inhibitors, highlighting the need for targeted immunotherapies like cancer vaccines. This review indicates the recent progress of four principal vaccine platformsDNA, peptide-based, dendritic cell (DC), and mRNA vaccinesfor BC immunotherapy. DNA vaccines offer rapid, cost-effective neoantigen delivery with plasmid engineering, showing promise in preclinical models and early trials (e.g., NCT03199040), particularly when combined with checkpoint blockade and developed and optimized a novel polyepitope neoantigen DNA vaccine platform that can target multiple neoantigens and induce antitumor immune responses. Peptide vaccines, exemplified by NeuVax (E75) and DPX-0907, demonstrate significant clinical benefits like improved disease-free survival (89.7% at 5 years), but require adjuvants and strategies to counter immunosuppressive cells. DC vaccines, evolving towards cDC1 utilization and neoantigen targeting, effectively prime CD4 and CD8 T-cell responses in patients, showing potential for preventing recurrence. mRNA vaccines, propelled by innovations like lipid nanoparticles (LNPs) and self-amplifying RNA (saRNA), enable efficient antigen expression in dendritic cells and potent immunogenicity, with preclinical synergy observed when combined with checkpoint inhibitors. While each platform shows significant preclinical and early clinical feasibility and immunogenicity, translating this into consistent robust clinical responses in advanced BC remains challenging. Key hurdles include tumor heterogeneity, immunosuppressive microenvironments, optimal antigen selection, and delivery optimization. Realizing the full potential of BC vaccines necessitates overcoming these barriers through refined platform engineering and strategic combinations with other immunotherapies.