Computational Prediction and Experimental Validation of Esophageal Cancer Associated Neoantigens

Esophageal Cancer Clinical Trial

Official title:

Computational Prediction and Experimental Validation of Esophageal Cancer Associated Neoantigens

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05498168
• Other study ID #: 61/GCN-HDDD
• Status: Not yet recruiting
• Start date: September 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2022
• Source: University Medical Center Ho Chi Minh City (UMC)
• Contact: Long Vo Duy, PhD
• Phone: +84.8.39525656
• Email: long.vd[@]umc.edu.vn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Genetic:
• ratio of predicted neoantigens
10 ml of whole blood is collected from each patient prior surgery Fresh tumor tissue samples (~ 1cm3 ) are collected during surgery

Locations

Country	Name	City	State
Vietnam	University Medical Center Ho Chi Minh City	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Ho Chi Minh City (UMC)

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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