ArticleSignal transduction and targeted therapy2026
Efficacy and immunomodulatory effect of Claudin18.2-specific IL-7/XCL1 armored CAR-T cells in digestive tract cancer: preclinical and clinical analysis.
Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- Next-generation CAR-T engineering for colorectal cancer: integrating targets, tumor microenvironment barriers, and emerging strategies.Frontiers in immunology · 2026Review
- Resistance mechanisms and countermeasures in CLDN18.2-positive tumors: from molecular networks to clinical practice.Frontiers in oncology · 2026Review
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR)-T cell therapy exerts limited therapeutic efficacy in solid tumors including digestive tract cancer (DTC), which is largely attributable to the suppressive tumor microenvironment (TME) and the functional deficits of CAR-T cells. Herein, we generated fourth-generation CAR-T cells engineered to target Claudin18.2 (CLDN18.2) with concurrent secretion of IL-7 and XCL1, which are designated as ExCAR-T cells (also named RD07 cells in a clinical trial). The preclinical results demonstrated the remarkable and enduring suppressive effects of ExCAR-T cells on DTC growth in murine models through activating both the inherent of the administered CAR-T cells and robust endogenous immune cells anti-tumor response. Furthermore, we performed a clinical investigation for previous systemic treatment failed patients with DTC. RD07 therapy was well tolerated, and 7 out of 10 patients exhibited tumor regression; this effect was particularly evident in patients exhibiting moderate to high CLDN18.2 expression (DCR of 100%). Finally, single-cell RNA (scRNA) sequencing combined with spatial landscape profiling revealed that RD07 has antitumor effects and activates endogenous immune cells within the TME. Concomitantly, enhanced cytotoxic activity of CAR-T cells and expanded T cell receptor (TCR) clonotypes were detected in patients with a partial response (PR). Taken together, present data demonstrate the therapeutic efficacy and safety of RD07 in our study and highlight its ability to both exert antitumor effects and remodel the TME. These findings support RD07 as an innovative CAR-T cell therapy for DTC.
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