A new CAR-T cell immunotherapy shows promising results against digestive cancers

Digestive tract cancers are among the deadliest worldwide and often resist conventional treatments such as surgery, radiotherapy, or chemotherapy. A recent breakthrough in immunotherapy could change the landscape. Researchers have developed a new generation of CAR-T cells, modified to specifically target a protein called Claudin18.2, which is frequently present on the surface of stomach and pancreatic cancer cells. These cells, called ExCAR-T, have the unique ability to release two molecules, IL-7 and XCL1, which stimulate both their own activity and the patient’s immune system.

Laboratory tests on mice have shown that these ExCAR-T cells significantly reduce tumor growth and extend the animals’ survival. Their effectiveness lies in their ability to attract and activate other immune cells, particularly dendritic cells and T lymphocytes, thereby creating a tumor microenvironment more conducive to the destruction of malignant cells. Unlike conventional CAR-T cells, ExCAR-T cells persist longer in the body and limit tumor escape mechanisms.

A clinical trial conducted on ten patients with advanced digestive cancers, for whom conventional treatments had failed, confirmed these encouraging results. Seven out of ten patients saw their tumors regress, especially those whose cancer cells strongly expressed the Claudin18.2 protein. No serious side effects were observed, and inflammatory reactions remained manageable. In-depth analyses revealed that ExCAR-T cells durably activate the body’s natural immune defenses, thereby enhancing their ability to fight the disease.

This innovative approach opens a promising avenue for patients suffering from refractory digestive cancers. It combines direct action against the tumor and overall stimulation of the immune system, offering an alternative to existing therapies, which are often insufficient. The results suggest that this immunotherapy could become a treatment of choice, particularly for aggressive and metastatic forms of these cancers.

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Official Study Source

DOI: https://doi.org/10.1038/s41392-026-02621-8

Title: Efficacy and immunomodulatory effect of Claudin18.2-specific IL-7/XCL1 armored CAR-T cells in digestive tract cancer: preclinical and clinical analysis

Journal: Signal Transduction and Targeted Therapy

Publisher: Springer Science and Business Media LLC

Authors: Xuan Zhao; Jinyan Liu; Zhen Zhang; Yali Zhou; Shuiling Jin; Hong Zong; Feng Wang; Min Song; Yali Zhong; Qinglong Li; Bo Pei; Yong Yu; Ming Gao; Wengang Ge; Lu Han; Jiangtao Ren; Yi Zhang