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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The Human Epithelial Cell Adhesion Molecule (EpCAM) is a Type I transmembrane glycoprotein consisting of two epidermal growth factor-like domains, one cysteine-poor region, one transmembrane domain and one short cytoplasmic tail. In normal cells and tissues, EpCAM expression is limited and the glycoprotein is shielded by tight junctions which limit its accessibility. In contrast, in tumor cells EpCAM is expressed on the whole cell surface, and thus becomes more accessible for binding. It is one of the most frequently and strongly expressed tumor-associated antigens in a number of tumor types including ovarian, gastric, colon, pancreatic, prostate, lung, and endometrial carcinoma. In particular, EpCAM is expressed on the vast majority of the main epithelial cancers that cause malignant ascites.
Serrated Polyposis Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Cancers affecting the colon and rectum (i.e., colorectal cancer) represent the third most common malignancy and the third leading cause of cancer-related death worldwide. Although many colorectal cancer cases arise sporadically, about 30% show a family history, and only 5% are clearly linked to hereditary disorders, including Lynch syndrome (mutated MLH1, MSH2, MSH6, PMS2, or EpCAM), familial adenomatous polyposis (FAP, mutated APC), MUTYH-associated polyposis (MAP, mutated MUTYH), juvenile polyposis syndrome (JPS, mutated STK11), Peutz−Jeghers syndrome (PJS, mutated SMAD4 or BMPR1A), hereditary mixed polyposis syndrome (HMPS, mutated GREM1), and serrated polyposis syndrome (SPS, mutated RNF43 and other genes) [4–8].
Circulating Tumor Cells in Individualizing Breast Cancer Therapy
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
James M. Reuben, Massimo Cristofanilli
EpCAM, also known as human epithelial cell antigen (HEA) or CD326, is expressed on the majority of tumor cells of epithelial cell origin but not on circulating B cells, T cells, or monocytes. In another assay that exploits this characteristic of CTCs, peripheral blood mononuclear cells are incubated with magnetic beads coated with anti-CD326 (Miltenyi Biotec, Inc., Auburn, California, U.S.) prior to passage through a magnetic column to enrich for CTCs. Typically, mononuclear cells are isolated from peripheral blood, bone marrow, pleural fluid, paracentesis fluid, or other tissues, mixed with anti-CD326 microbeads, and incubated at 4°C to 8°C for 15 minutes. After washing, the cell pellet is resuspended and loaded onto the magnetic column of an automatic magnetic cell sorting (AutoMACS™) system (Miltenyi Biotec) (25). CD326-positive CTCs are isolated using the positive selection protocol and can then be centrifuged onto glass slides to determine the morphology, viability, and purity of the preparation.
Pathologic and Immunophenotypic Characterization of Syncytial Giant Cell Variant of Pediatric Hepatocellular Carcinoma. A Distinct Subtype
Published in Fetal and Pediatric Pathology, 2023
Mukul Vij, Jagadeesh Menon, Komalavalli Subbiah, Lexmi Priya Raju, Gowripriya Gowrisankar, Naresh Shanmugum, Ilankumaran Kaliamoorthy, Ashwin Rammohan, Mohamed Rela
EpCAM is a transmembrane glycoprotein, expressed on tumor-initiating cells, progenitor/stem cells and cancers [30]. EpCAM shows circumferential membranous expression in all cases (100%) of pHCC as compared to adults where it is only focally expressed in 15% [17]. All pediatric cases had chronic liver diseases (tyrosineima, BSEP and biliary atresia) [17]. Explanations for such an exuberant EpCAM expression in pHCC include a large number of cancer progenitor/stem cells, biliary differentiation, or immature nature of neoplastic cells. EpCAM is also connected to Wnt–β-catenin signaling pathway, and both play a role in the maintenance of hepatic cancer stem cells [30]. Both our cases showed diffuse cytoplasmic AFP immunostaining. AFP immunohistochemical sensitivity is low in HCC (30%) and majority of positive cases show patchy staining [31]. EpCAM and AFP positive adult HCC patients have a poor prognosis [32]. Although no such data is available for pHCC, extrapolating from the adult cohort, we propose these patients will require close follow-up for early recurrence. Eight-month follow-up is available for both kids and they are doing well.
Efficacy of epi-1 modified epirubicin and curcumin encapsulated liposomes targeting-EpCAM in the inhibition of epithelial ovarian cancer cells
Published in Journal of Liposome Research, 2023
Yu-Jia Wang, Ling Tang, Xu-Hong Lu, Ji-Tao Liu, Yuan-Yuan Wang, Hong-Xia Geng, Xue-Tao Li, Quan An
Among these systems, liposomes are noticeable attractive drug delivery system that not only encapsulate hydrophilic and hydrophobic drugs, but also increase blood circulation time, thereby improving drug delivery efficiency in TME (Jung et al.2010, Xin et al.2021). Liposomes composed of phospholipids and cholesterol have unique properties, including improved drug stability, excellent biocompatibility, reduced drug toxicity, and their tunable surface modifications, which offer many advantages over other drug carriers (Zununi Vahed et al.2017). Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is expressed exclusively in epithelial cells and epithelial-derived tumors and was found to be overexpressed on cancer cells isolated from patients with EOC by immunohistochemical studies (Zheng et al.2017). EpCAM has been found to be involved in cell proliferation, migration, invasion, and differentiation and plays an important role in cancer metastasis, suggesting that it could be a molecular therapeutic target for EOC (Muynck et al.2020). Epi-1 (D-WRPTRURLLPWWICGSGSK) is a macrocyclic peptide with high affinity and specific binding to EpCAM, and modification on the surface of lipid nanoparticles can enhance active drug targeting and improve cellular uptake of drugs (Iwasaki et al.2015, Sakurai et al.2017).
Combined targeting of soluble latent TGF-ß and a solid tumor-associated antigen with adapter CAR T cells
Published in OncoImmunology, 2022
Niels Werchau, Bettina Kotter, Elvira Criado-Moronati, Andre Gosselink, Nicole Cordes, Dominik Lock, Simon Lennartz, Carolin Kolbe, Nora Winter, Karin Teppert, Fabian Engert, Brian Webster, Joerg Mittelstaet, Daniel Schaefer, Peter Mallmann, Michael R. Mallmann, Dominik Ratiu, Mario Assenmacher, Thomas Schaser, Michael von Bergwelt-Baildon, Pierre Abramowski, Andrew D. Kaiser
To evaluate the spatial distribution and co-localization of latent TGF-β with markers of the TME, ovarian cancer tissue was chosen and analyzed via MICS. The expression pattern of LAP, as a surrogate for latent TGF-β, was evaluated on ovarian tissue specimens of two cancer patients. Both patients suffered from cancer with tumor cells being characterized by EpCAM expression. By comparing tumor-rich (Figure 1) and tumor-free regions (S.1, 2 B), we were able to analyze the co-localization of LAP with the expression pattern of 94 surface markers (Table S.1). Areas invaded by tumor cells showed clear visual segregation from tumor-free tissue parts. Areas surrounding the tumor were characterized by dense CD49a expression in conjunction with CD90. LAP expression was strongly overlapping with CD90 and CD49a in desmoplastic areas surrounding EpCAM+ tumor cells. By calculating the Pearson correlation coefficient (PCC) of three regions of interest (ROIs) showing EpCAM+ tumor cells we could show that CD90 (PCC: 0.32 ± 0,08) and CD49a expression (PCC: 0.35 ± 0,04) was linearly increasing with LAP expression in these areas (Figure 1C). In contrast, in three ROIs without EpCAM expression these markers showed a markedly reduced linear correlation with LAP expression (CD49a: 0.11 ± 0,04; CD90: 0.13 ± 0,05) (S.1 C). These findings indicate that latent TGF-β is a potential antigen for CAR T cells to target desmoplastic areas of solid tumors.