Identification of Tumor Specific Neoantigens and Their Implications in Dendritic Cell Immunotherapy Using Liquid Biopsy Results: Findings from an Observational Cohort Study
Abstract Liquid biopsies can be a rapid, cost-effective and noninvasive alternative to tumor biopsies for detecting genetic mutations in somatic tumors. Genetic profiling of liquid biopsies can also be used to identify novel antigens for targeted therapy, provide updated information on disease prognosis and evaluate treatment efficacy. In this study, we aimed to examine mutations that could be identified in liquid biopsy and their potential implications for personalized dendritic cell immunotherapy using these antigens. We analyzed the genomic profiles of 99 blood samples from 85 patients with 22 different types of cancer using two commercially available liquid biopsy tests before the patients underwent standard cancer treatment and dendritic cell immunotherapy. Nonsynonymous mutations were detected in more than 90% of the samples, with an average frequency of 3.6 mutations per sample. The tumor mutations were specific to each patient, as approximately 94.7% of the mutations were so unique that there was almost no duplication among the patients. Clonal evolution was observed in two patients just before or after chemotherapy, radiotherapy and immunotherapy. These findings indicate that liquid biopsy can be a potential surrogate for tumor-specific antigen-based immunotherapy and the importance of tailoring immunotherapy in accordance with the liquid biopsy result in each treatment stage.