A recent Nature Reviews Immunology study discusses challenges associated with the development and design of neoantigen cancer vaccines.
Study: Challenges in developing personalized neoantigen cancer vaccines. Image Credit: Lightspring / Shutterstock.com
Development of cancer therapy using neoantigens
Several genetic factors are associated with cancer manifestations, including DNA mutations, deletion, fusions, and translocation. It is imperative to understand the process of tumorigenesis to identify potential targets essential for developing effective cancer therapies.
After genomic mutations of cancer cells, altered or new protein products are generated. These proteins are antigenically novel for the host and referred to as neoantigens, which are recognized as foreign by the host immune system. Based on neoantigens, several immunotherapies, such as adoptive T-cell therapies and immune checkpoint blockade (ICB) therapy, have been developed.
Cancer-associated neoantigens have been used to develop therapeutic vaccines that specifically target the tumor without affecting healthy tissues. Most clinical cases exhibit endogenous T-cell responses induced by these vaccines, which are unable to control the proliferation of cancer cells. Thus, there remains an urgent need for new therapeutic vaccines that can enhance or induce T-cell responses against neoantigens and improve anticancer immunity.
Smaller clinical trials of many neoantigen vaccines, including NCT03897881 for melanoma and NCT04161755 for pancreatic cancer, have shown promise for future use. However, before commercialization, several challenges associated with these vaccines must be addressed to optimize their safety and efficacy.
Challenges of developing effective neoantigen cancer vaccines
The efficacy of any vaccine depends on the immunogenicity of its antigen. Next-generation sequencing (NGS) provides