This study is to develop computational pipelines and experimental validation assays for improving the identification of neoantigens from patients with esophageal cancer.
Esophageal cancer (EC) is the common malignant tumor with poor survival. The long-term surival rate of patients with advanced EC stages has not been improved with multidisciplinary treatments including surgery and chemotherapy and radiation. Recently, immunotherapy approaches using checkpoint inhibitors (CPI), cancer vaccine, and adoptive T cell therapy have improved survival outcomes of EC patients. The clinical outcomes are associated with expression levels as well as the immunogenicity of neoantigens which arise from soma mutations. Therefore, the identification of immunogenic neoantigens is essential for achieving effective therapies. Recent data published by the Tumor Neoantigen Selection Alliance (TESLA) show that the majority (98%) of predicted neoantigens are lack of immunogenicity and ineffective in activating antitumor immune responses. In our study, we aim to develop a pipeline with both computational prediction tools and experimental validation assays to enhance the accuracy of neoantigen identification.
Study Type
OBSERVATIONAL
Enrollment
50
10 ml of whole blood is collected from each patient prior surgery Fresh tumor tissue samples (\~ 1cm3 ) are collected during surgery
University Medical Center Ho Chi Minh City
Ho Chi Minh City, Vietnam
The neoantigen landscape of patients with esophageal cancer
The analysis of tumor DNA and RNA sequencing data will provide the mutational distribution of patients with esophageal cancer, which could give rise to neoantigens. Of those, neoantigens derived from hotspot mutations in Vietnamese esophageal cancer patients will be identified.
Time frame: 3 months from the begining of study
The ratio of predicted neoantigens being presented by HLA-I
Computational pipelines will be employed to predict the pairing of neoantigens and HLA molecules. Subsequently, the ratio of those predicted neoantigens will be validated by co-immunoprecipitation with anti-HLA antibodies and mass spectrometry analysis for their binding to corresponding HLA molecules.
Time frame: 6 months from the begining of study
The ratio of predicted neoantigens being immunogenic
Immunoassays will be employed to identify neoantigens that could activate CD4 and CD8 T cells to kill tumor cells and serve as putative candidates for immunotherapy.
Time frame: 12 months from the begining of study
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.