Neoepitopes-based vaccines: challenges and perspectives

Area of Science:

• Immunology
• Oncology
• Vaccinology

Background:

• Early cancer vaccines using shared tumor antigens yielded limited clinical success.
• The advent of immune checkpoint inhibitors has revitalized interest in cancer vaccines targeting neoantigens.

Purpose of the Study:

• To review the renewed interest in anti-tumoral vaccination based on mutation-associated neoantigens.
• To discuss the potential of neoantigen vaccines in combination with immune checkpoint inhibitors and in adjuvant settings.
• To highlight challenges and future directions in neoantigen vaccine development.

Main Methods:

• Review of current literature on cancer vaccines, neoantigens, and immune checkpoint inhibitors.
• Analysis of clinical trial data and preclinical research findings.
• Discussion of immunological mechanisms and resistance pathways.

Main Results:

• First-generation cancer vaccines showed disappointing clinical outcomes.
• Neoantigen-based vaccines demonstrate encouraging early clinical activity and induce specific immune responses.
• Vaccination can enhance responses to Programmed cell death 1 (PD-1/-L1) inhibitors and prime T-cell responses in 'cold' tumors.
• Adjuvant vaccination may offer long-term control of residual disease.

Conclusions:

• Neoantigen-based cancer vaccines represent a promising therapeutic strategy, particularly when combined with immune checkpoint inhibitors.
• Challenges remain in predicting effective neoepitopes and understanding resistance mechanisms.
• Further research is needed to clarify the role of CD4+ T cells and explore novel neoantigen sources.