EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors

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.