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3 results on '"Ting-Yen Lai"'

1. Increased expression of SSEA-4 on TKI-resistant non-small cell lung cancer with EGFR-T790M mutation.

Author

Nai-Yu Chen, Chih-Wei Lin, Ting-Yen Lai, Chung-Yi Wu, Pei-Chi Liao, Tsui-Ling Hsu, and Chi-Huey Wong

Subjects
NON-small-cell lung carcinoma, PROTEIN-tyrosine kinase inhibitors
Abstract

Non-small cell lung cancer (NSCLC), a major life-threatening disease accounting for 85% of all lung cancer cases, has been treated with tyrosine kinase inhibitors (TKIs), but often resulted in drug resistance, and approximately 60% of TKI-resistant cases are due to acquired secondary (epithelial growth factor receptor) EGFR-T790M mutation. To identify alternative targets for TKI-resistant NSCLC with EGFR-T790M mutation, we found that the three globo-series glycosphingolipids are increasingly expressed on this type of NSCLC cell lines, and among them, the increase of stage-specific embryonic antigen-4 (SSEA-4) expression is the most significant. Compared to TKI-sensitive cell lines, SSEA-4 and the key enzyme ß3GalT5 responsible for the synthesis of SSEA3 are more expressed in TKI-resistant NSCLC cell lines with EGFR-T790M mutation, and the expression levels strongly correlate with poor survival in patients with EGFR mutation. In addition, we demonstrated that a SSEA-4 targeted monoclonal antibody, especially the homogeneous glycoform with well-defined Fc glycan designed to improve effective functions, is highly effective against this subpopulation of NSCLC in cell-based and animal studies. These findings provide a direction for the prediction of tumor recurrence and treatment of TKI-resistant NSCLC with EGFR-T790M mutation. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Combined Effect of Anti-SSEA4 and Anti-Globo H Antibodies on Breast Cancer Cells

Author

Ting-Yen Lai, Tsui-Ling Hsu, Chi-Huey Wong, Ruey-Herng Lee, Yu-Jen Wang, Po-Kai Chuang, and Han-Chung Wu

Subjects
Stage-Specific Embryonic Antigens, Breast Neoplasms, Biochemistry, Antibodies, Article, Mice, Breast cancer, Antigen, ADCC assay, Cell Line, Tumor, medicine, Animals, Humans, Antigens, Tumor-Associated, Carbohydrate, skin and connective tissue diseases, Antibody-dependent cell-mediated cytotoxicity, biology, Chemistry, Receptors, IgG, General Medicine, medicine.disease, In vitro, Killer Cells, Natural, Homogeneous, Cancer research, biology.protein, Molecular Medicine, Breast cancer cells, Antibody
Abstract

The globo-series glycosphingolipids (SSEA3, SSEA4, and Globo H) were shown to express in many cancers selectively, and a combination of anti-SSEA4 and anti-Globo H antibodies was able to suppress tumor growth in mice inoculated with breast cancer cell lines. To further understand the effect, we focused on the combined effect of the two antibodies in target binding and antibody-dependent cellular cytotoxicity (ADCC) in vitro. Here, we report that the binding of anti-Globo H antibody (VK9) to MDA-MB231 breast cancer cells was influenced by anti-SSEA4 antibody (MC813-70), and a combination of both antibodies induced a similar effect as did anti-SSEA4 antibodies alone in a reporter-based ADCC assay, indicating that SSEA4 is a major target in breast cancer due to its higher expression than Globo H. Furthermore, we showed that a homogeneous anti-SSEA4 antibody (chMC813-70-SCT) designed to maximize the ADCC activity can be used to isolate a subpopulation of natural killer (NK) cells that exhibit an ∼23% increase in killing the target cells as compared to the unseparated NK cells. These findings can be used to predict a therapy outcome based on the expression levels of antigens and evaluate therapeutic antibody development.

Published
2021

3. Homogeneous antibody and CAR-T cells with improved effector functions targeting SSEA-4 glycan on pancreatic cancer

Author

Chih-Wei Lin, Yu-Jen Wang, Ting-Yen Lai, Tsui-Ling Hsu, Shin-Ying Han, Han-Chung Wu, Chia-Ning Shen, Van Dang, Ming-Wei Chen, Lan-Bo Chen, and Chi-Huey Wong

Subjects
Stage-Specific Embryonic Antigens, Multidisciplinary, Cell- and Tissue-Based Therapy, Mice, Nude, Biological Sciences, Immunotherapy, Adoptive, Xenograft Model Antitumor Assays, Antibodies, Pancreatic Neoplasms, Mice, Gene Expression Regulation, Cell Line, Tumor, embryonic structures, Animals, Humans, Immunotherapy
Abstract

Pancreatic cancer is usually asymptomatic in the early stages; the 5-y survival rate is around 9%; and there is a lack of effective treatment. Here we show that SSEA-4 is more expressed in all pancreatic cancer cell lines examined but not detectable in normal pancreatic cells; and high expression of SSEA-4 or the key enzymes B3GALT5 + ST3GAL2 associated with SSEA-4 biosynthesis significantly lowers the overall survival rate. To evaluate potential new treatments for pancreatic cancer, homogeneous antibodies with a well-defined Fc glycan for optimal effector functions and CAR-T cells with scFv construct designed to target SSEA-4 were shown highly effective against pancreatic cancer in vitro and in vivo. This was further supported by the finding that a subpopulation of natural killer (NK) cells isolated by the homogeneous antibody exhibited enhancement in cancer-cell killing activity compared to the unseparated NK cells. These results indicate that targeting SSEA-4 by homologous antibodies or CAR-T strategies can effectively inhibit cancer growth, suggesting SSEA-4 as a potential immunotherapy target for treating pancreatic disease.

Published
2021

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