開發新型雙功能抗體以強化T細胞毒殺高表現表皮生長因子受體三陰性乳癌之功效

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Title:	開發新型雙功能抗體以強化T細胞毒殺高表現表皮生長因子受體三陰性乳癌之功效 Development of novel bispecific antibody to enhance therapeutic effect of T cells against EGFR-expressing triple negative breast cancer
Authors:	李依庭 Lee, Yi-Ting
Contributors:	臨床藥物基因體學暨蛋白質體學碩士學位學程莊國祥
Keywords:	三陰性乳腺癌(Triple Negative Breast Cancer);MDA-MB-231;新型雙功能抗體;PBMC(Peripheral Blood Mononuclear Cell);T 細胞;雙功能抗體培育之T 細胞(Antitumoe Arm-T cell)平台 Triple Negative Breast Cancer (TNBC);bispecific antibody (BsAbs);efficiently differentiate, highly expand;Armed-T cells;MDA-MB-231
Date:	2018-12-28
Issue Date:	2020-01-20 13:05:46 (UTC+8)
Abstract:	三陰性乳癌(Triple Negative Breast Cancer)於臨床表徵為ER (Estrogen receptor)、PR (Progesterone receptor)以及HER2 (Human Epidermal Growth Factor Receptor 2) 皆呈陰性之乳癌種類1,2，目前仍以化學療法為主要治療方式，其五年存活率僅62%。為提供三陰性乳癌更佳之治療，本實驗室開發新型雙功能抗體培育T細胞療法平台(Anti-tumor Armed-T cell)，於活體外培育周邊血單核球細胞 (Peripheral Blood Mononuclear Cell，PBMC)過程添加新型雙功能抗體，使周邊血單核球細胞可於10天內快速增殖、分化並轉變為具抗原專一性之CD3+CD8+ T細胞(Anti-tumor Armed-T cell)，以提升T細胞對腫瘤專一性毒殺。研究結果顯示，我們利用蛋白質工程技術成功建構出新型雙功能抗體，並藉流式細胞儀確認其與三陰性乳癌細胞(MDA-MB-231，EGFR+)以及T細胞(CD3+)之雙邊結合能力，並確認T細胞增殖、分化為CD3+CD8+ T細胞之效果，且於活體外證實Anti-tumor Arm-T cell細胞具專一性快速辨認，並釋放細胞激素/毒素，以提升毒殺並抑制三陰性乳癌細胞(MDA-MB-231，EGFR+)生長之能力。本研究開發一全新T細胞療法治療策略，藉由新型anti-EGFR/anti-CD3雙功能抗體一步驟武裝、分化並增殖成為具腫瘤專一性之T細胞。 Triple Negative Breast Cancer (TNBC) is corresponded to 15 to 20 % of all breast cancer diagnosis in women. Anthracycline and taxane-based chemotherapy are the mainly treatment for TNBC in clinical; however, the lack of effective target led to worse 5-year overall and disease-free survival rate with 62% and 57.5%. Therefore, novel treatment for TNBC is urgent needed. In our previous study, we have developed the novel ex vivo bispecific antibody (BsAb) cultured platform for T cells (Anti-tumor Arm-T cell), in which T cells were cultured with BsAb that is combined with anti-tumor antibody to anti-CD3 antibody, making Peripheral Blood Mononuclear Cells (PBMCs) have the ability to differentiate efficiently, highly expand to Anti-tumor Arm-T cell with the selective function to eliminate cancer cells in the same time. We successfully construct the novel BsAb and ensure the bispecific function by TNBC cell line (MDA-MB-231,EGFR+)and T cell (CD3+).Moreover, Anti-tumor Arm-T cell could rapidly recognize MDA-MB-231 as soon as possible and release cytokines to elevate the ability to eliminate tumor cells in vitro and in vivo study. To summarize, our study provides a novel adoptive T cell therapy (Anti-tumor Arm-T cell) with rapid differentiating, expanding, and arming human T cells by adding novel BsAb into human PBMC culture medium and enhancing the ability of T cells to target the TNBC.
Description:	碩士指導教授：莊國祥委員：鄒協成委員：卓爾婕
Data Type:	thesis
Appears in Collections:	[Master Program for Clinical Pharmacogenomics and Pharmacoproteomics] Dissertations/Theses

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