Title : Application of CTCs for biomarker development of immunotherapies
Abstract:
I mmunotherapies with chimeric antigen receptor-modified T (CAR-T) cells and Immune Checkpoint Inhibitors (ICIs) have shown exhilarative clinical outcome in treating Cancers. When applying CAR-T-based and ICIs-based immunotherapies for treating solid tumors, detection of expressions of targeting antigens on tumor tissues with IHC assays is required. For example, MSLN and PD-L1 detection with IHC assays for MSLN-CAR-T-based and PD1-based immunotherapies, respectively. However, assays on tumor tissue specimens can be limited by age, quality, and resection of patients. Thus, CTCs collected from blood can be used for detection of expressions of targeted antigens on tumor cells, and the concentration of PD-L1 that has been used as biomarkers for PD-1-based immunotherapies. In our work, we explored and validated the application of CTCs as standard biomarker for CAR-T-based and PD-1-based immunotherapies. Mesothelin, EGFR, MUC1, MMR, and PD-L1 were analyzed in CTCs for relative CAR-T cell-based therapies. And DNA from CTCs can be used for ctDNA sequencing for TMB and targeted therapy tests.