BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
This article is part of the Research TopicAdvancements and Challenges in CAR-T Cell Therapy for Cancer TreatmentView all 5 articles
CCR2 improves tumor directed CAR-T cell trafficking in ovarian cancer
Provisionally accepted
- 1Massachusetts General Hospital Cancer Center, Boston, United States
- 2Harvard Medical School, Boston, United States
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Solid tumors present a significant challenge to Chimeric Antigen Receptor (CAR) -T cell therapy, primarily due to limited T-cell infiltration and persistence in the tumor microenvironment. Cancers with predominantly peritoneal metastasis like ovarian cancer pose a substantial trafficking challenge to systemically administered CAR-T cell therapy. To identify chemokines that may guide CAR-T cells to tumor sites, we evaluated chemokine expression in primary and metastatic tumor samples from patients with ovarian cancer by immunohistochemistry. After identifying CCL2 as the most common chemokine expressed in both primary and metastatic disease, we validated CCL2 levels in serum samples from these patients. We found that CCL2 and CCL4 were commonly expressed in several ovarian cancer cell lines, a patient-derived tumor cell line and patient serum samples in vitro. We engineered armed Muc16/CA-125-directed CAR-T cells with cognate receptors for CCL2 and CCL4 and showed significant in vitro and in vivo tumor-directed trafficking. Finally, intravenously administered CCL2-armored CAR-T cells significantly prolonged survival in peritoneal tumor bearing mice. In conclusion, we identified CCL2 as a commonly expressed chemokine in patients with local and metastatic ovarian cancer and successfully demonstrate that armed CAR-T cells with enhanced homing to CCL2-expressing ovarian cancer are more efficacious due to improved peritoneal trafficking in vivo.
Keywords: ovarian cancer, MUC16, Chimeric antigen receptor T-cells, CAR-T cells, Armed CAR-T cells, Chemokines
Received: 21 Jun 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Kumar, Veillard, Al-Alem, Rueda and Yeku. 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: Oladapo Yeku
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