An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer

Liao, Mei Ying; Lai, Ji-Ching; Kuo, Mark Yen‐Ping; Lu, Ruei Min; Lin, Cheng; Cheng, Ping; Liang, Kang-Hao; Wu, Han-Chung

doi:10.18632/oncotarget.4453

Cited by 42 publications

(39 citation statements)

References 80 publications

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“…45,46 Additionally, a few studies using anti-EpCAM antibody showed that it might have an anti-tumour effect. [47][48][49] However, the validation of EpCAM as a therapeutic target remains unexplored.…”

Section: Discussionmentioning

confidence: 99%

Expression of EpCAM in adenoid cystic carcinoma

et al. 2018

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The mutational landscape of adenoid cystic carcinoma (ACC) is currently being revealed, but further studies are needed to identify biomarkers as therapeutic targets or prognostic factors of ACC. In this study, we investigated the expression of epithelial cell adhesion molecule (EpCAM) in ACCs. We retrospectively collected 83 cases of surgically resected ACCs. Using tissue microarray, we conducted immunohistochemical staining using the anti-EpCAM antibody. EpCAM expression was analysed by intensity score and the total immunostaining score. The positivity was 97.6% (81/83 cases), regardless of the intensity score. A higher histological grade (p = 0.006) and specific tumour location (non-salivary gland origin, p = 0.02) showed a correlation with higher EpCAM intensity. Higher EpCAM expression by total immunostaining score was associated with histological grade (p = 0.004), distant metastasis (p = 0.004) and poorer prognosis (overall survival p = 0.015 and progressionfree survival p = 0.033). We suggest EpCAM as a candidate prognostic marker and a putative therapeutic target in ACC. Also, ACCs arising from salivary gland and non-salivary gland sites, respectively, might display different pathophysiologies in which EpCAM could play a role.

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Section: Discussionmentioning

confidence: 99%

Expression of EpCAM in adenoid cystic carcinoma

et al. 2018

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“…Firstly, antibody-binding could be harmful to cell survival. Some antibodies against EpCAM, for example, may directly cause cancer cell death [79] or indirectly induce antibody-dependent cell-mediated cytotoxicity (ADCC). Indeed, anti-EpCAM mediated cancer cell killing is a mechanism sought in studies involving adecatumumab, edrecolomab and catumaxomab.…”

Section: Technical Issues In the Various Ctc Isolation Methodsmentioning

confidence: 99%

Cultured circulating tumor cells and their derived xenografts for personalized oncology

Wang

Chu

Mrđenović

et al. 2016

Asian Journal of Urology

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Recent cancer research has demonstrated the existence of circulating tumor cells (CTCs) in cancer patient's blood. Once identified, CTC biomarkers will be invaluable tools for clinical diagnosis, prognosis and treatment. In this review, we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample, to derive enough CTCs for accurate and reproducible characterization of the biophysical, biochemical, gene expressional and behavioral properties of the harvested cells. Because of tumor cell heterogeneity, it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis. By analyzing critical steps and technical issues in ex vivo CTC culture, we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells, relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells.

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“…Overexpression of EpCAM results in highly upregulated oncogene expression and promotes cell proliferation [ 16 ]. With the development of molecular technologies, EpCAM has gained attention as a potential target for diagnostic and antibody-based immunotherapies for a spectrum of malignancies [ 17 ]. The treatment improved the survival rate by 30% and decreased the recurrence rate by 27% over 7 years of evaluation [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

Zhang

Ding

et al. 2018

Journal of Immunology Research

114

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Adoptive chimeric antigen receptor-modified T or NK cells (CAR-T or CAR-NK) offer new options for cancer treatment. CAR-T therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. However, their therapeutic efficacy against solid tumors is limited. New regimens, including combinations with chemical drugs, need to be studied to enhance the therapeutic efficacy of CAR-T or NK cells for solid tumors. An epithelial cell adhesion molecule- (EpCAM-) specific second-generation CAR was constructed and transduced into NK-92 cells by lentiviral vectors. Immune effects, including cytokine release and cytotoxicity of the CAR-NK-92 cells against EpCAM-positive colon cancer cells, were evaluated in vitro. Synergistic effects of regorafenib and CAR-NK-92 cells were analyzed in a mouse model with human colorectal cancer xenografts. The CAR-NK-92 cells can specifically recognize EpCAM-positive colorectal cancer cells and release cytokines, including IFN-γ, perforin, and granzyme B, and show specific cytotoxicity in vitro. The growth suppression efficacy of combination therapy with regorafenib and CAR-NK-92 cells on established EpCAM-positive tumor xenografts was more significant than that of monotherapy with CAR-NK-92 cells or regorafenib. Our results provided a novel strategy to treat colorectal cancer and enhance the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.

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An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer

Cited by 42 publications

References 80 publications

Expression of EpCAM in adenoid cystic carcinoma

Expression of EpCAM in adenoid cystic carcinoma

Cultured circulating tumor cells and their derived xenografts for personalized oncology

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

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