A Phase II, Open Label, Multiple Center Study of huC242-DM4 Given as an Intravenous Infusion Once Every Three Weeks to Patients With Metastatic Gastric or Gastroesophageal Junction Carcinomas

To assess the response rate of huC242-DM4 given as an intravenous infusion to patients with metastatic or locally advanced gastric or gastroesophageal junction cancer.

开始日期2007-05-01

申办/合作机构

ImmunoGen, Inc.

NCT00352131 / Completed临床1期

A Phase I Study to Assess the Safety and Pharmacokinetics of huC242-DM4 Administered as a Single Intravenous Infusion Once Every Three Weeks to Subjects With Solid Tumors

RATIONALE: Monoclonal antibodies, such as maytansinoid DM4-conjugated humanized monoclonal antibody huC242, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of maytansinoid DM4-conjugated humanized monoclonal antibody huC242 in treating patients with solid tumors that cannot be removed by surgery or have spread to other parts of the body.

开始日期2005-02-01

申办/合作机构

ImmunoGen, Inc.

100 项与 CanAg 相关的临床结果

登录后查看更多信息

100 项与 CanAg 相关的转化医学

登录后查看更多信息

0 项与 CanAg 相关的专利（医药）

登录后查看更多信息

项与 CanAg 相关的文献（医药）

2015-06-01·Molecular Pharmaceutics2区 · 医学

Sensitive ELISA Method for the Measurement of Catabolites of Antibody–Drug Conjugates (ADCs) in Target Cancer Cells

2区 · 医学

Article

作者: Singh, Rajeeva ; Salomon, Paulin L.

A new, sensitive ELISA method has been developed which measures catabolites in cells and media upon processing of antibody-drug conjugates (ADCs) by target cancer cells. This ELISA method, exemplified for maytansinoid ADCs, uses competitive inhibition by a maytansinoid analyte of the binding of biotinylated antimaytansine antibody to an immobilized BSA-maytansinoid conjugate. Synthetic standards of several maytansinoid catabolites derived from ADCs with different linkers were tested and showed similar inhibition curves, with an EC50 of about 0.1 nM (0.03 pmol in an assay volume of 0.25 mL). This high sensitivity allowed quantification of catabolites from a methanolic cell extract and from the medium, generated from an ADC in 1 day using only about 1 million cells. The processing of anti-EpCAM and anti-CanAg ADCs with noncleavable linker (SMCC-DM1), disulfide linker (SPDB-DM4), and charged sulfonate-bearing disulfide linker (sulfo-SPDB-DM4), each containing an average of about four maytansinoid molecules per antibody, were compared in colon cancer cell lines (COLO 205 and HT-29). An 8-10-fold higher total level of catabolite was observed for anti-CanAg ADCs than for anti-EpCAM ADCs upon processing by COLO 205 cells, consistent with a higher cell-surface expression of CanAg. In a multidrug resistant HCT-15 colon cancer cell line, the anti-EpCAM-SPDB-DM4 linker conjugate was not cytotoxic and showed a significantly lower level of catabolite within cells compared to that in medium, presumably due to Pgp-mediated efflux of the nonpolar DM4 catabolite. In contrast, sulfo-SPDB-DM4 and SMCC-DM1 linker conjugates were cytotoxic, which correlated with higher amounts of catabolites found within the HCT-15 cells relative to amounts in medium. In a nonmultidrug resistant HT-29 cell line, the anti-EpCAM-SPDB-DM4 linker conjugate was cytotoxic, with most of the catabolite found in cells and little in the medium. In conclusion, this highly sensitive ELISA method for measurement of ADC catabolite is convenient for screening multiple ADC parameters such as linkers and antibodies in a number of cell lines, does not require concentration of sample or extraction of media, and is complementary to other reported methods such as radiolabeling of ADCs or mass spectrometry.

2014-01-01·Journal of Cellular Biochemistry3区 · 生物学

HSF1 and Sp1 Regulate FUT4 Gene Expression and Cell Proliferation in Breast Cancer Cells

3区 · 生物学

Article

作者: Yan, Qiu ; Wang, Jiao ; Liu, Shuiai ; Yang, Xuesong

ABSTRACTLewis Y (LeY) is a carbohydrate tumor‐associated antigen. The majority of cancer cells derived from epithelial tissues express LeY type difucosylated oligosaccharides. Fucosyltransferase IV (FUT4) is an essential enzyme that catalyzes the synthesis of LeY oligosaccharides. In a previous study we reported that FUT4 is associated with cell proliferation; however, despite the important role of FUT4 in cancer proliferation and apoptosis, little is known about the mechanisms underlying the regulation of FUT4 transcription. In the current study we investigated the regulation of FUT4 transcription in human breast cancer. We compared the regulation of human FUT4 gene transcription in human breast cancer cells (MCF‐7 and MDA‐MB‐231) using promoter/luciferase analyses. Using a series of promoter deletion constructs, we identified a potential regulatory site located between 0.8 and 1.6 kb of the FUT4 promoter. As shown by EMSA and ChIP analyses, heat‐shock factor 1 (HSF1) and Sp1are required for FUT4 promoter activity. In addition, we explored the role of HSF1 and Sp1 on cell proliferation, and found that the ERK1/2 MAPK and PI3K/Akt signaling pathways regulate the expression of FUT4, which play a role in cell proliferation via HSF1 and Sp1. These results suggest that FUT4 is a target gene for HSF1 and Sp1 that is required for cell cycle progression in breast cancer epithelial cells. J. Cell. Biochem. 115: 168–178, 2014. © 2013 Wiley Periodicals, Inc.

2013-11-01·Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences

[Anti-sTn antibody 3P9 and B72.3 in serological diagnosis of endometrial carcinoma].

Article

作者: Guo, Shangyun ; Zhai, Xuhua ; Sun, Haibin ; Yang, Xiaohui ; Meng, Fang ; Fu, Jianhong ; Chen, Xiuqin ; Guo, Qi

OBJECTIVETo investigate the relationship between tumor-associated carbohydrate antigen sTn and endometrial carcinoma, and to evaluate the diagnostic value of 2 test methods.METHODSA total of 200 patients were enrolled, including 100 subjects with endometrial carcinoma, 42 healthy nonpregnant women, 15 pregnant women without complications, and 43 patients with benign gynecologic diseases. The serum sTn-antigen concentrations were determined by 2 test methods (3P9 combined with 4A6, and B72.3 combined with CC49).RESULTSThere was a significant difference in the value and the positive rate of sTn in the serum between the subjects and the contrasts (P<0.05). The sTn level in the pregnant women was high. The sTn level in the serum and its positive rate in endometrial carcinoma became higher with the clinical stage. 3P9 combined with 4A6 was better than B72.3 combined with CC49 in the detection of sTn in the serum as to sensitivity, specificity, positive-prediction, negative-prediction, and accuracy.CONCLUSIONThe sTn antigen may become a new serological marker for the diagnosis of endometrial carcinoma, but pregnant women should be excluded. 3P9 combined with 4A6 is better than B72.3 combined with CC49 in the detection of sTn in the serum.