Computational Prediction and Experimental Validation of Esophageal Cancer Associated Neoantigens

This study is to develop computational pipelines and experimental validation assays for improving the identification of neoantigens from patients with esophageal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Cancer; Neoantigen
• Intervention / Treatment: Genetic: ratio of predicted neoantigens

Detailed Description

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 (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Long Vo Duy, PhD; Phone Number: +84.8.39525656; Email: long.vd@umc.edu.vn
• Study Contact Backup: Name: Thong Dang Quang; Email: thong.dq@umc.edu.vn

Study Locations

• Vietnam
  • Ho Chi Minh City, Vietnam, 700000
    • University Medical Center Ho Chi Minh city

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All the patients who were diagnosed with adavanced esophageal cancer and underwent surgical resection

Description

Inclusion Criteria:

1. Male or Female patients aged 18 years and older
2. Diagnosed with advanced esophageal cancer
3. Treatment-Naive
4. Not known for other concomitant cancers
5. Provide written informed consent

Exclusion Criteria:

1. Insufficient tumor tissues (less than 1 cm3 )
2. Unable to sign informed consent
3. Underwent treatment

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	12 months from the begining of study

Collaborators and Investigators

• Sponsor: University Medical Center Ho Chi Minh City (UMC)

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: 61/GCN-HDDD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No