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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1539055
This article is part of the Research Topic Innovative Therapeutic Approaches for Complex Cancers: Exploring New Strategies in Glioblastoma, Urogenital, and Bladder Cancers View all 4 articles
Enhanced anti-tumor efficacy of "IL-15 and CCL19" -secreting CAR-T cells in human glioblastoma orthotopic xenograft model
Provisionally accepted
Wanqiong Chen 1
Limian Hong 2 Shaomei Lin 1 Na Xian 3 Cailing Yan 4 Ningning Zhao 5 Yonglei Xiao 3 Wanting Liao 1 Yuxiang Huang 1
Mingzhu Chen 1*- 1 School of Pharmacy, Quanzhou Medical College, Quanzhou, Fujian, China
- 2 Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, China
- 3 Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, China
- 4 Public Technology Service Center, Fujian Medical University, Fuzhou, Fujian, China
- 5 Laboratory Animal Center, Fujian Medical University, Fuzhou, Fujian, China
Despite the remarkable success of CAR-T cell therapy in hematologic malignancies, its progress in solid tumors has been slow. Overcoming challenges such as the recruitment and infiltration of CAR-T cells into the tumor site and the survival issues in the harsh tumor microenvironment are crucial for successful application in solid tumors. In this study, CAR-T cells were engineered to secrete both IL-15 and CCL19, and their efficacy was evaluated in a human glioblastoma orthotopic xenograft model. we designed CAR-T cells with the ability to secrete both IL-15 and CCL19 and investigated their efficacy in a human glioblastoma orthotopic xenograft model. Our The results reveal that 15 × 19 CAR-T cells exhibit superior proliferation, chemotaxis, and phenotypic characteristics compared to conventional CAR-T cells in vitro. In vivo, 15 × 19 CAR-T cells exhibit superior control over tumors compared to conventional counterparts. Mechanistically, the improved efficacy can be attributed, in part, to IL-15 and CCL19 enhancing T-cell infiltration at the tumor site and fortifying resistance to exhaustion within the tumor microenvironment. In conclusion, the incorporation of IL-15 and CCL19 into CAR-T cells emerges as a promising strategy to elevate the anti-tumor efficacy of CAR-T cell therapy, positioning 15 × 19 CAR-T cells as a potential breakthrough for enhancing the application of CAR-T therapy in solid tumors.
Keywords: CAR-T cells, Glioblastoma, IL-15, CCL19, cancer immunotherapy, EGFRv III
Received: 03 Dec 2024; Accepted: 28 Feb 2025.
Copyright: © 2025 Chen, Hong, Lin, Xian, Yan, Zhao, Xiao, Liao, Huang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mingzhu Chen, School of Pharmacy, Quanzhou Medical College, Quanzhou, Fujian, China
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