By Kim Polacek, APR, CPRC - November 05, 2023
Personalized cancer vaccines to treat cancer are an emerging area of cancer research. This type of therapy engages the immune system’s cells to attack a tumor by exposing them to unique proteins or antigens expressed by a cancer cell. The vaccines have shown promise in the treatment of solid tumor malignancies, but there continues to be a need to optimize this complex therapeutic approach.
Moffitt Cancer Center researchers are working to improve the efficacy of neoantigen-targeted cancer vaccines by better understanding whether primary or metastatic tumors should be used to produce the personalized vaccine. They launched a study evaluating primary and metastatic tumors pairs from 45 patients with several solid tumor types, including melanoma, bladder, head and neck cancers, and non-small cell lung cancer. Whole exome sequencing was used to identify somatic alterations, which are genetic mutations or DNA alterations that may impact the type of antigens produced by the cancer cells that can then be targeted by the vaccine.
Results presented at the Society for Immunotherapy of Cancer annual meeting show that melanoma, bladder and head and neck tumors share a high percentage of mutations between primary and metastatic tumors. However, other solid tumors, such as esophageal and non-small cell lung cancer, share less.
“Our analysis demonstrates genetic variations that exist when comparing paired primary and metastatic tumors that appear to vary by histology. Variants are potentially undergoing negative selection supported by the preferential loss of out-of-frame events in metastatic tumors,” said Dr. Ahmad Tarhini, senior member in the Departments of Cutaneous Oncology and Immunology and director of Cutaneous Clinical and Translational Research at Moffitt. Understanding the clonal structure will be key to neoantigen prediction for effective neoantigen-based vaccines where oncogenic drivers can be prioritized and used to determine the primary clones.”
Tarhini and the Moffitt team are continuing this work, expanding their study to include paired tumor samples from 600 additional patients.