EpCAM-targeted induction of apoptosis

Bremer, Edwin; Helfrich, Wijnand

doi:10.2741/3062

Cited by 3 publications

(4 citation statements)

References 57 publications

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“…BCYRN1 is just a promoter upstream transcript of its neighboring protein coding gene EpCAM [ 21 ]. EpCAM has been shown to exert critical functions in cell proliferation, differentiation, apoptosis and migration of diverse cell types [ 22 , 32 – 34 ] and it also plays an important role in GC development [ 35 – 38 ]. In this study, we hypothesized that BCYRN1 might regulate EpCAM and could thus exert similar effects on GC cells.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma

Ren

Yang

et al. 2017

Oncotarget

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Brain cytoplasmic RNA 1 (BCYRN1), along non-coding RNA, plays a critical role in various diseases, including some cancers. However, the expression of BCYRN1 and its roles in gastric carcinoma (GC) still remain unidentified. Thus, this study employed RT-qPCR to detect expression of BCYRN1 in 85 paired GC samples and adjacent normal tissues, and performed in vitro studies to explore effects of BCYRN1 in GC cells on cell proliferation, apoptosis and migration. We found BCYRN1 was significantly upregulated in GC samples, and its expression was positively correlated with advanced TNM stage (p = 0.0012) and tumor size (p = 0.027). Functionally, BCYRN1 knockdown by siRNA could inhibit cell proliferation, induce G1/G0 cell cycle arrest, increase apoptosis and impair migratory ability of AGS cells. Moreover, the results of RT-qPCR and western blotting indicated that knockdown of BCYRN1 notably decreased the expression of epithelial cell adhesion molecules (EpCAM). Otherwise, overexpression of BCYRN1 in GC cells (BGC-823 and SGC-7901) could reverse the effects of BCYRN1 knockdown. Taken together, our data indicate for the first time that BCYRN1 acts as an oncogenic lncRNA in GC progression and may be a potential therapeutic target in GC.

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Section: Discussionmentioning

confidence: 99%

Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma

Ren

Yang

et al. 2017

Oncotarget

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“…An increased cytotoxicity through targeting requires a simultaneous binding of the antibody-TRAIL fusion proteins to the target antigen and TRAIL receptors, i.e. a spatial co-localization either on the same or neighboring cells [ 16 ], which might be less efficient for the fusion protein directed against EpCAM.…”

Section: Discussionmentioning

confidence: 99%

“…Through binding to cell surface structures, the fusion protein is delivered to target cells and, in addition, mimics the membrane-bound form of TRAIL capable of activating TRAIL-R2. Most commonly, TRAIL has been combined with scFvs directed against tumor-associated antigens (TAA) to directly kill target-positive tumor cells in cis as well as target-negative cancer cells in trans through a bystander effect [ 16 ]. Furthermore, scFvs targeting the tumor vasculature or immune cells have been employed to either disrupt tumor supply or to equip immune cells with additional cytotoxic activity.…”

Section: Introductionmentioning

confidence: 99%

Targeting scFv-Fc-scTRAIL fusion proteins to tumor cells

et al. 2018

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“…EpCAM shows high potential as a target for developing anticancer therapies and immunotherapies with monoclonal antibodies or bispecific antibodies. Recent studies have targeted EpCAM with monoclonal antibodies [11], bispecific antibodies, immunotherapy [12], siRNA, and CAR-T cells [5,[13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

mRNA-Lipid Nanoparticle (LNP) Delivery of Humanized EpCAM-CD3 Bispecific Antibody Significantly Blocks Colorectal Cancer Tumor Growth

Golubovskaya

Sienkiewicz

Sun

et al. 2023

Cancers

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The epithelial cell adhesion molecule (EpCAM) is often overexpressed in many types of tumors, including colorectal cancer. We sequenced and humanized an EpCAM mouse antibody and used it to develop bispecific EpCAM-CD3 antibodies. Three different designs were used to generate bispecific antibodies such as EpCAM-CD3 CrossMab knob-in-hole, EpCAM ScFv-CD3 ScFv (BITE), and EpCAM ScFv-CD3 ScFv-human Fc designs. These antibody designs showed strong and specific binding to the EpCAM-positive Lovo cell line and T cells, specifically killed EpCAM-positive Lovo cells and not EpCAM-negative Colo741 cells in the presence of T cells, and increased T cells’ IFN-gamma secretion in a dose-dependent manner. In addition, transfection of HEK-293 cells with EpCAM ScFv-CD3 ScFv human Fc mRNA-LNPs resulted in antibody secretion that killed Lovo cells and did not kill EpCAM-negative Colo741 cells. The antibody increased IFN-gamma secretion against Lovo target cells and did not increase it against Colo741 target cells. EpCAM-CD3 hFc mRNA-LNP transfection of several cancer cell lines (A1847, C30, OVCAR-5) also demonstrated functional bispecific antibody secretion. In addition, intratumoral delivery of the EpCAM-CD3 human Fc mRNA-LNPs into OVCAR-5 tumor xenografts combined with intravenous injection of T cells significantly blocked xenograft tumor growth. Thus, EpCAM-CD3 hFc mRNA-LNP delivery to tumor cells shows strong potential for future clinical studies.

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EpCAM-targeted induction of apoptosis

Cited by 3 publications

References 57 publications

Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma

Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma

Targeting scFv-Fc-scTRAIL fusion proteins to tumor cells

mRNA-Lipid Nanoparticle (LNP) Delivery of Humanized EpCAM-CD3 Bispecific Antibody Significantly Blocks Colorectal Cancer Tumor Growth

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