Jeffrey Weber, MD, PhD, NYU Langone Health, New York, NY, discusses the historical development and clinical potential of neoantigens in cancer therapy. He explains that neoantigens, typically single nucleotide variants unique to cancer cells, have been shown to elicit clinical benefits. This was initially demonstrated in a landmark study by Steve Rosenberg at the National Cancer Institute, which found that neoantigen-specific tumor-infiltrating lymphocytes could mediate clinical responses. He also highlights two pioneering studies from 2017: one by Kathy Wu and Patrick Ott at Dana-Farber using peptide vaccines, and another by BioNTech employing an RNA-based approach, both showing immunogenicity and early signs of clinical efficacy. Prof. Weber additionally discusses the Phase II KEYNOTE-942 trial (mRNA-4157-P201) (NCT03999749), where updated results reaffirm the benefits of combining an individualized neoantigen vaccine with pembrolizumab, demonstrating significant improvements in recurrence-free and distant metastasis-free survival compared to pembrolizumab alone. This interview took place during the 2024 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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