EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab

Lan Yu; Qing-Ming Guo; Yu Wang; Yan Xu; Li Liu; Xiao-Tao Zhang

doi:10.21037/jtd-21-442

EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab

J Thorac Dis. 2021 Apr;13(4):2404-2413. doi: 10.21037/jtd-21-442.

Authors

Lan Yu¹, Qing-Ming Guo², Yu Wang¹, Yan Xu¹, Li Liu¹, Xiao-Tao Zhang¹

Affiliations

¹ Department of Stereotactic Radiotherapy, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, China.
² Biotherapy Center, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, China.

Abstract

Background: Recurrence of esophageal cancer (EC) after chemotherapy may mainly be explained by the existence of chemotherapy-resistant cells, and an effective drug against chemotherapy-resistant cells is highly sought. The aim of this study was to investigate the cytotoxicity of bispecific antibody solitomab combined with γ δ T cells on Eca109 cell spheres.

Methods: We cultured Eca109 cell spheres in serum-free medium, and the morphological differences between wild-type Eca109 cells and Eca109 cell spheres were compared by microscope and flow cytometry. Different concentrations of nanoparticle albumin-bound paclitaxel (Nab-PTX) and cisplatin were used to treat the two groups of cells and compare their drug resistance. Flow cytometry was then used to detect the expression level of epithelial cell adhesion molecule (EpCAM) and the cytotoxicity of γ δ T cells combined with bispecific antibody solitomab on the two groups.

Results: Flow cytometry analysis showed that Eca109 cell spheres were smaller in size and had less cytoplasmic granules and CCK-8 assay showed that the viability of Eca109 cell spheres treated with different concentrations of Nab-PTX and cisplatin was significantly higher than that of wild-type Eca109 cells (P<0.05). Flow cytometry also showed that the expression level of EpCAM on Eca109 cell spheres was higher than that of wild-type Eca109 cells. Co-culture experiment showed that there was no significant difference in the cytotoxicity of γ δ T cells to wild-type Eca109 cells and Eca109 cell spheres without solitomab. However, after adding solitomab, the cytotoxicity of γ δ T cells to Eca109 cell spheres was significantly higher than that of wild-type Eca109 cells (P<0.05).

Conclusions: EC Eca109 cell spheres have strong stem cell characteristics such as multidrug resistance and may contain a high proportion of EC stem cells. Further, EC Eca109 cell spheres have a high expression level of EpCAM, and EpCAM may be one of the markers of EC stem cells. Therefore, EpCAM could be used as a potential molecular target of immunotherapy for EC, and solitomab may become an effective immunotherapeutic drug for chemotherapy-resistant EC cells.

Keywords: Esophageal cancer (EC); cancer stem cell (CSC); epithelial cell adhesion molecule (EpCAM); solitomab.