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Published on: February 21, 2025
EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors
Dan Li1, Xianling Guo2, Kun Yang3
1Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
The efficacy of CAR-T cells for solid tumors is unsatisfactory. EpCAM is a biomarker of epithelial tumors, but the clinical feasibility of CAR-T therapy targeting EpCAM is lacking. Here, we report pre- and clinical investigations of EpCAM-CAR-T cells for solid tumors. We demonstrated that EpCAM-CAR-T cells costimulated by Dectin-1 exhibited robust antitumor activity without adverse effects in xenograft mouse models and EpCAM-humanized mice. Notably, in clinical trials for epithelial tumors (NCT02915445), 6 (50%) of the 12 enrolled patients experienced self-remitted grade 1/2 toxicities, 1 patient (8.3%) experienced reversible grade 3 leukopenia, and no higher-grade toxicity reported. Efficacy analysis determined two patients as partial response. Three patients showed >23 months of progression-free survival, among whom one patient experienced 2-year progress-free survival with detectable CAR-T cells 200 days after infusion. These data demonstrate the feasibility and tolerability of EpCAM-CAR-T therapy.
Insights
Chimeric antigen receptor T-cell (CAR-T) therapy targeting EpCAM shows promise for solid tumors. Pre-clinical and clinical studies indicate EpCAM-CAR-T cells are feasible and tolerable, with some patients achieving partial responses and extended progression-free survival.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- CAR-T cell therapy has shown limited efficacy in solid tumors.
- Epithelial cell adhesion molecule (EpCAM) is a promising biomarker for epithelial tumors.
- Clinical application of EpCAM-targeted CAR-T therapy is underdeveloped.
Purpose of the Study:
- To investigate the pre-clinical and clinical efficacy and safety of EpCAM-CAR-T cells for solid tumors.
- To evaluate the anti-tumor activity and tolerability of Dectin-1 costimulated EpCAM-CAR-T cells.
Main Methods:
- Pre-clinical studies in xenograft mouse models and EpCAM-humanized mice.
- Clinical investigation (NCT02915445) in patients with epithelial tumors.
- Assessment of anti-tumor activity, toxicity, and progression-free survival.
Main Results:
- EpCAM-CAR-T cells demonstrated robust anti-tumor activity with no adverse effects in mouse models.
- In clinical trials, 50% of patients had self-remitted grade 1/2 toxicities, and 8.3% had reversible grade 3 leukopenia.
- Two patients achieved partial response, and three had >23 months progression-free survival, including one with 2-year PFS.
Conclusions:
- EpCAM-CAR-T cell therapy is feasible and tolerable for solid tumors.
- Dectin-1 costimulation enhances the anti-tumor activity of EpCAM-CAR-T cells.
- The study supports further clinical development of EpCAM-CAR-T therapy for epithelial malignancies.
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