Exploring the therapeutic efficacy difference in claudin18.2-targeted cell therapy revealed by single-cell sequencing
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Published on: May 22, 2017
Mingyang Ma1, Chang Liu2, Lei Jiang1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing 100142, China.
Abstract:
Chimeric antigen receptor T cell (CAR T) therapy has been successfully used to treat hematological malignancies. Nonetheless, its application to solid tumors remains challenging. Our previous analysis of the ongoing clinical trial (NCT03874897) demonstrated promising results in patients with advanced CLDN18.2-positive gastric cancer who received CT041 CAR T treatment. Here, we collected peripheral blood and ascites from five patients from the clinical trial 3 and 7 days (d) after CT041 infusion. Patients with a high proportion of naïve-like T cells were more likely to benefit from CT041 treatment. We found that high expression of CLDN18 in ascites epithelial cells correlated with a favorable prognosis, whereas ascites epithelial cells with high MYC expression and strong interactions between tumor cells and T cells were adverse prognostic factors for CT041 treatment. These findings may provide theoretical evidence for the screening of populations that can benefit from CAR T therapy and improve the efficacy of CAR T therapy.
Insights
Chimeric antigen receptor T (CAR T) therapy shows promise for gastric cancer. Naïve-like T cells and CLDN18 expression predict treatment success, while MYC and tumor-T cell interactions indicate poor outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Chimeric antigen receptor T (CAR T) therapy is effective against blood cancers but faces challenges in solid tumors.
- Previous studies of NCT03874897 showed positive outcomes for CT041 CAR T treatment in advanced CLDN18.2-positive gastric cancer.
Purpose of the Study:
- To investigate prognostic factors influencing CT041 CAR T therapy efficacy in gastric cancer patients.
- To identify biomarkers for patient selection and potential strategies to enhance CAR T therapy outcomes.
Main Methods:
- Collected peripheral blood and ascites samples from five gastric cancer patients post-CT041 infusion (3 and 7 days).
- Analyzed the proportion of naïve-like T cells, CLDN18 expression in ascites, MYC expression, and tumor-T cell interactions.
Main Results:
- A higher proportion of naïve-like T cells correlated with better response to CT041 treatment.
- High CLDN18 expression in ascites epithelial cells predicted a favorable prognosis.
- High MYC expression in ascites epithelial cells and strong tumor-T cell interactions were associated with adverse outcomes.
Conclusions:
- Findings suggest that naïve-like T cell proportion and CLDN18 expression are favorable prognostic indicators for CAR T therapy in gastric cancer.
- MYC expression and tumor-T cell interactions may represent negative prognostic factors.
- These results offer a basis for refining patient selection and improving CAR T therapy efficacy in solid tumors.
