作者: Saijou, Shinji ; Yano, Tomonori ; Yasunaga, Masahiro ; Fujita, Takeo ; Sasabe, Maasa ; Mitsunaga, Shuichi ; Yamaguchi, Toru ; Koga, Yoshikatsu ; Sakashita, Shingo ; Ishikawa, Akihiro ; Yang, Shiqi ; Tanaka, Hideki ; Yoda, Yusuke ; Takashima, Kenji ; Anzai, Takahiro

ABSTRACT:

Near‐infrared photoimmunotherapy (NIR‐PIT) is a tumor‐specific treatment using monoclonal antibody (mAb) photosensitizer conjugates, followed by near‐infrared light irradiation. This study aimed to identify the optimum target for treating esophagogastric junction (EGJ) adenocarcinoma and to evaluate the efficacy of NIR‐PIT using mAbs in preclinical models. Tumor samples from 46 consecutive patients who had undergone surgery without any prior treatment for EGJ adenocarcinoma were assessed for expression and homogeneity of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and epithelial cell adhesion molecule (EpCAM) through immunohistochemistry. Results showed positive rates of 22%, 13%, and 98% for EGFR, HER2, and EpCAM, respectively, with EpCAM also demonstrating the highest homogeneity (93%). Therefore, EpCAM was selected as the optimal target for NIR‐PIT. The fully human monoclonal antibody targeting EpCAM, adecatumumab, was conjugated with the photosensitizer IR700 at different dye‐antibody ratios (DAR2, DAR4, DAR7) and tested on OE19 cells and xenograft mouse models under near‐infrared light irradiation. NIR‐PIT with adecatumumab‐IR700 significantly reduced tumor size and improved prognoses compared to controls, with DAR2 showing the best balance of efficacy and minimal side effects. Notable EpCAM expression and homogeneity underpin EpCAM as a promising target for NIR‐PIT in EGJ adenocarcinoma. The fully human anti‐EpCAM antibody may be suitable for NIR‐PIT in EGJ adenocarcinoma.

2024-12-01·PLANT CELL REPORTS

Plant-derived EpCAM-Fc fusion proteins induce in vivo immune response to produce IgGs inhibiting invasion and migration of colorectal cancer cells

Article

作者: Oh, Yoojin ; Kim, Kibum ; Hinterdorfer, Peter ; Lee, Hyun Jung ; Kang, Eunjeong ; Hwang, Hyunjoo ; Lim, Sohee ; Lee, Daehwan ; Kim, Yerin ; Ko, Kisung ; Cho, Sayeon

KEY MESSAGE:

Transgenic tobacco plant expressed EpCAM-Fc fusion proteins to induce in vivo immune responses producing anti-EpCAM antibodies inhibiting human colorectal cancer cell invasion and migration. Plant is emerging as a promising alternative to produce valuable immunotherapeutic vaccines. In this study, we examined the in vivo anti-cancer efficacy of epidermal cell adhesion molecule (EpCAM)-Fc and EpCAM-FcK fusion proteins produced in transgenic plants as colorectal cancer vaccine candidates. Mice were injected with plant-derived EpCAM-Fc (EpCAM-Fc^P) and EpCAM-Fc^P tagged with KDEL (ER retention signal) (EpCAM-FcK^P), using mammalian-derived EpCAM-Fc (EpCAM-Fc^M) as positive control. Total IgGs from the immunized mice were used to assess immune responses. ELISA tests revealed that IgGs from mice immunized with EpCAM-FcK^P (EpCAM-FcK^P IgG) exhibited the highest absorbance value for binding affinity to recombinant EpCAM-Fc^M compared to IgGs from mice immunized with EpCAM-Fc^P (EpCAM-Fc^P IgG) and EpCAM-Fc^M (EpCAM-Fc^M IgG). Bio-layer interferometry revealed that EpCAM-FcK^P IgG had a higher affinity value than EpCAM-Fc^M IgG and EpCAM-Fc^P IgG. Cell ELISA revealed that EpCAM-FcK^P IgG exhibited the highest binding activity to EpCAM-positive cells SW480 and SW620 compared to EpCAM-Fc^P IgG, EpCAM-Fc^M IgG, and anti-EpCAM mAb. In the transwell invasion assay, EpCAM-FcK^P IgG significantly decreased the numbers of invaded SW480 and SW620 cells compared to EpCAM-Fc^P IgG, whereas EpCAM-Fc^M IgG had similar numbers. In the wound healing assay, EpCAM-FcK^P IgG showed higher migration inhibition compared to EpCAM-Fc^P IgG in both cell types, with similar results to EpCAM-Fc^M IgG in SW620 cells. These results confirm the applicability of plant systems to produce EpCAM-Fc vaccine candidates, inducing the production of anti-EpCAM IgGs against colorectal cancer cells.

2021-01-01·Technology in cancer research & treatment4区 · 医学

A Modified Method to Isolate Circulating Tumor Cells and Identify by a Panel of Gene Mutations in Lung Cancer

4区 · 医学

ArticleOA

作者: Li, Zhuoran ; Hao, Jianqing ; Niu, Hongrui ; Zhang, Qi ; Wang, Ying ; Wu, Jieqing ; Zhang, Shucai ; Wang, Helin ; Zhang, Hongtao

The CellSearch system is the only FDA approved and successful used detection technology for circulating tumor cells(CTCs). However, the process for identification of CTCs by CellSearch appear to damage the cells, which may adversely affects subsequent molecular biology assays. We aimed to explore and establish a membrane-preserving method for immunofluorescence identification of CTCs that keeping the isolated cells intact. 98 patients with lung cancer were enrolled, and the efficacy of clinical detection of CTCs was examined. Based on the CellSearch principle, we optimized an anti-EpCAM antibody and improved cell membrane rupture. A 5 ml peripheral blood sample was used to enrich CTCs with EpCAM immunomagnetic beads. Fluorescence signals were amplified with secondary antibodies against anti-EpCAM antibody attached on immunomagnetic beads. After identifying CTCs, single CTCs were isolated by micromanipulation. To confirm CTCs, genomic DNA was extracted and amplified at the single cell level to sequence 72 target genes of lung cancer and analyze the mutation copy number variations (CNVs) and gene mutations. A goat anti-mouse polyclonal antibody conjugated with Dylight 488 was selected to stain tumor cells. We identified CTCs based on EpCAM+ and CD45+ cells to exclude white blood cells. In the 98 lung cancer patients, the detection rate of CTCs (≥1 CTC) per 5 ml blood was 87.76%, the number of detections was 1–36, and the median was 2. By sequencing 72 lung cancer-associated genes, we found a high level of CNVs and gene mutations characteristic of tumor cells. We established a new CTCs staining scheme that significantly improves the detection rate and allows further analysis of CTCs characteristics at the genetic level.

项与 anti-EpCAM antibody (Jiangsu hengrui) 相关的新闻（医药）

2023-10-24

·PipelineReview

EpCAM, a broadly expressed, validated cancer target rescued by novel antibody technologies

BARCELONA, Spain I October 24, 2023 I La Merie Publishing released its newest product reviewing the pipeline of anti-EpCAM antibody therapy candidates in R&D: EpCAM-Targeted Antibodies Pipeline Review Target: EpCAM (Epithelial Cell Adhesion Molecule) Product Category: Antibody This product provides basic information on antibody therapy candidates in research and development targeting EpCAM. This product consists of: This product is delivered on the very same day of purchase by e-mail containing competitor and project history reports in pdf format and database credentials. Reports are prepared on the same day. Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein mediating Ca2+-independent cell-cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, proliferation, and differentiation. Additionally, EpCAM has oncogenic potential via its capacity to upregulate c-myc and cyclins A & E. EpCAM is over-expressed in most of epithelial tumors including colon cancer (97.7%), gastric cancer (90.7%), prostate cancer (87.2%), and lung cancer (63.7%). The high-level expression of EpCAM in solid tumors has made it an attractive target for antibody molecules to treat epithelial cancers, particularly adenocarcinomas. However, EpCAM is also highly prevalent on normal cells. EpCAM is a broadly expressed, validated anti-cancer target that to date has been limited in its development potential due to systemic, on-target off-tumor dose-limiting toxicities. ADC target options are limited by normal tissue expression. Although EpCAM is an ideal cancer target, it has not been tractable by conventional approaches. Conditional activation can allow ADC technology and T-cell recruiting bispecific antibody technologies to be applied to a wider set of targets. Conventional EpCAM/CD3 bispecific antibodies have shown beneficial clinical outcomes in cancer patients, but have been hampered by dose limiting toxicities due to wide target distribution in normal tissues and potent T cell activation. The report “ EpCAM-Targeted Antibodies Pipeline Review ” can be acquired at La Merie Publishing’s online store: https://lamerie.com/report/epcam-targeted-antibodies-pipeline-review/ About La Merie Publishing La Merie Publishing is an independent business information provider for the biotechnology and pharmaceutical industry. La Merie Publishing prepares brief and full reports. La Merie Publishing products can be purchased in the online store www.lamerie.com and from selected Resellers. La Merie Publishing offers the service of custom report preparation for corporate clients, including, but not limited to, pipeline analysis reports, drug profiles and any other competitive intelligence elaboration of interest. SOURCE: La Merie Publishing

100 项与 anti-EpCAM antibody (Jiangsu hengrui) 相关的药物交易

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