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CXCL10 and IL15 co-expressing chimeric antigen receptor T cells enhance anti-tumor effects in gastric cancer by increasing cytotoxic effector cell accumulation and survival

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机构: [1]PLA Medical School, Beijing, China. [2]Research and Development Department, Beijing DCTY Biotech Co. LTD, Beijing, China. [3]Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. [4]Department of Functional Neurosurgery, Capital Medical University, Beijing, China. [5]Department of Functional Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China.
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关键词: CAR-T cells interleukin 15 CXCL10 infiltration Claudin18 2

摘要:
Chimeric antigen receptor (CAR) T cells have demonstrated outstanding therapeutic success in hematological malignancies. Yet, their efficacy against solid tumors remains constrained due to inadequate infiltration of cytotoxic T and CAR-T cells in the tumor microenvironment (TME), a factor correlated with poor prognosis in patients with solid tumors. To overcome this limitation, we engineered CAR-T cells to secrete CXCL10 and IL15 (10 × 15 CAR-T), which sustain T cell viability and enhance their recruitment, thereby amplifying the long-term cytotoxic capacity of CAR-T cells in vitro. In a xenograft model employing NUGC4-T21 cells, mice receiving 10 × 15 CAR-T cells showed superior tumor reduction and extended survival rates compared to those treated with second-generation CAR-T cells. Histopathological evaluations indicated a pronounced increase in cytotoxic T cell accumulation in the TME post 10 × 15 CAR-T cell treatment. Therefore, the synergistic secretion of CXCL10 and IL15 in these CAR-T cells enhances T cell recruitment and adaptability within tumor tissues, improving tumor control. This approach may offer a promising strategy for advancing CAR-T therapies in the treatment of solid tumors.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 肿瘤学
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出版当年[2022]版:
Q1 IMMUNOLOGY Q1 ONCOLOGY
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Q1 IMMUNOLOGY Q1 ONCOLOGY

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第一作者机构: [1]PLA Medical School, Beijing, China. [2]Research and Development Department, Beijing DCTY Biotech Co. LTD, Beijing, China. [3]Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
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