Immune Response to Neoantigens Sparks Research in Myeloma
Posted: Monday, January 27, 2020
Analyzing next-generation sequencing data in 184 patients with relapsed multiple myeloma, researchers completed reportedly the first study to experimentally validate the immunogenicity of predicted neoantigens. Their findings appeared in Clinical Cancer Research. According to senior author Samir Parekh, MD, of Tisch Cancer Institute at Mount Sinai in New York, and colleagues, their results lay the groundwork to use neoantigen-targeting strategies—potentially “cancer vaccines”—in future trials involving patients with multiple myeloma.
The process behind this precision immunotherapy strategy is based on how somatic mutations in cancer cells can engender novel protein sequences—in other words, mutated tumors can make byproducts, neoantigens. Once provoked, a host immune system may respond to neoantigens by recognizing and killing cancer cells, the authors described.
The multiple myeloma research involved several findings. First, Dr. Parekh and his team demonstrated a higher neoantigen load in relapsed compared with newly diagnosed patients. They then identified “shared neoantigens across multiple patients in three multiple myeloma oncogenic driver genes: KRAS, NRAS, and IRF4.” Further, they reported validation of “neoantigen T-cell response and clonal expansion in correlation with clinical response in relapsed patients.”
The researchers demonstrated that neoantigen-specific T-cell activation can be “associated with [both] antitumor activity in vitro and clinical response in vivo,” they wrote. “Our results provide the foundation for using neoantigen-targeting strategies such as peptide vaccines in future trials.”
Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.