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The Mechanism of Enhancing the Anti-tumor Effects of CAR-T on PC by Gut Microbiota Regulation

Pancreatic Cancer Clinical Trial

Official title:
Study on the Mechanism of Enhancing the Anti-tumor Effects of Human Chimeric Antigen Receptors T Cells on Pancreatic Cancer by Gut Microbiota Regulation

Clinical Trial Summary

Pancreatic cancer (PC) is one of the deadliest diseases of human digestive malignancies. Despite the recent advances in surgery and chemotherapy, the 5-year survival rate of PC continues to be less than 10%. As a promising tumor therapy,Chimeric antigen receptor T cell (CAR-T), however, performed poorly in PC treatment and need to be further updated. In our study, on the basis of our previous research, we use anti-MSLN CAR-T as effector cell and explore the different effects and mechanism of gut microbiota (PC or healthy control) on anti-MSLN CAR-T treatment. Firstly, we detect the differences of gut microbiota and T cell cholesterol metabolism in PC and healthy control by means of 16S-rRNA,PCR, western blot and ELISA; explore the different effects of gut microbiota on the subtype of T cells; and analyze the relationships between intestinal flora composition and T cell cholesterol metabolism or subtype changes by means of Spearman's correlation. Secondly, we also explore the different effects of gut microbiota on the proliferation, migration, subtype, inflammatory cytokines expression and anti-tumor effector function of anti-MSLN CAR-T cells by means of flow cytometry and cytotoxicity assay. Thirdly, we discuss the different expression of cholesterol esterification enzyme 1 (ACAT-1) and other core genes of cholesterol metabolism in anti-MSLN CAR-T. Lastly, we evaluate the effects of different gut microbiota on the treatment of PC by anti-MSLN CAR-T cells in NSG mouse model of subcutaneous PC transplantation and liver metastasis. Through the above experiments, a new theoretical basis is provided in which gut microbiota regulates the subtype and anti-tumor function of anti-MSLN CAR-T by ACAT-1 expression. Furthermore, our findings, which demonstrate the relationship of gut microbiota and CAR-T cell, may be translatable for the treatment of other solid tumors like PC.

Clinical Trial Description

n/a

Study Design

Related Conditions & MeSH terms

Clinical Trial Details
NCT number NCT04203459
Study type Observational [Patient Registry]
Source First Affiliated Hospital of Harbin Medical University
Contact Yunwei Wei
Phone +860451-85553099
Email hydwyw11@hotmail.com
Status Recruiting
Phase
Start date October 20, 2019
Completion date December 31, 2022
View Details
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