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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
- Source :
- OncoImmunology, Vol 13, Iss 1 (2024)
- Publication Year :
- 2024
- Publisher :
- Taylor & Francis Group, 2024.
-
Abstract
- ABSTRACTChimeric 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.
Details
- Language :
- English
- ISSN :
- 2162402X
- Volume :
- 13
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.80f99c7722d84e7b94875e9937f114c8
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/2162402X.2024.2358590