[Modification with IL-21 and CCL19 enhances killing efficiency and tumor infiltration of NKP30 CAR-T cells in lung cancer]
- 1Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
- 2School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350100, China.
- 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
- 4Department of Thoracic Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
- 5Department of Thoracic Oncology Radiation, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
- 0Laboratory of Immuno-Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
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View abstract on PubMed
Summary
This summary is machine-generated.Engineered NKP30 CAR-T cells, modified with IL-21 and CCL19, show enhanced lung cancer cell killing and tumor infiltration. These modified cells also promote the generation of memory T cells for sustained anti-tumor immunity.
Area Of Science
- Immunotherapy
- Oncology
- Cellular Engineering
Context
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- Chimeric antigen receptor (CAR)-T cell therapy has shown promise but faces challenges in solid tumors.
- NKP30 CAR-T cells target the B7H6 ligand, highly expressed on lung cancer cells.
Purpose
- To investigate the efficacy of modifying NKP30 CAR-T cells with IL-21 and CCL19.
- To assess the impact of this modification on tumor cell killing and infiltration in lung cancer.
- To evaluate the in vivo performance of these engineered cells in a zebrafish xenograft model.
Summary
- IL-21 and CCL19 fusion gene modified NKP30 CAR-T cells were constructed and characterized.
- These modified cells demonstrated superior proliferation, migration, and killing of lung cancer cells compared to unmodified CAR-T cells.
- Reduced CTLA4 and PD1 expression and increased IFN-γ, IL-21, and CCL19 secretion were observed, alongside memory T cell formation.
Impact
- The IL-21 and CCL19 modification enhances the anti-tumor activity of NKP30 CAR-T cells against lung cancer.
- This strategy improves CAR-T cell infiltration into solid tumors, leading to more effective tumor cell killing.
- The generation of memory T cells suggests potential for durable anti-cancer responses.
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