新型膀胱癌標記物有助抗癌藥物開發

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　　　導讀：中科院生物物理研究所范祖森研究組最近在腫瘤學研究權威期刊Clinical Cancer Research雜志發表了題為BCMab1, a monoclonal antibody against aberrantly glycosylated Integrin a3b1, has potent antitumor activity of bladder cancer in vivo的研究論文介紹了一種全新的膀胱癌腫瘤標志物異常糖基化的整合素分子a3b1，這種分子可作為一個全新的膀胱癌腫瘤標志物。其特異性抗體BCMab1及抗體毒素偶聯物BCMab1-Ra具有顯著的靶向抑瘤作用。

　　范祖森等人篩選到了一株高特異性的抗膀胱癌單克隆抗體BCMab1，其識別的抗原表位是異常糖基化修飾的整合素a3b1。a3b1只表達于人膀胱腫瘤的細胞膜上，并與膀胱癌的腫瘤分期和病理分級呈正相關。BCMab1單抗特異性識別異常糖基化修飾的整合素a3b1分子，能有效地抑制腫瘤細胞的增殖、遷移、粘附和侵襲。該BCMab1抗體通過ADCC和ADCP作用，介導NK細胞和巨噬細胞對腫瘤的清除作用。BCMab1單抗膀胱灌注裸鼠原位模型能夠明顯抑制腫瘤的生長，BCMab1與蓖麻子毒素偶聯的抗體毒素藥物（BCMab1-Ra）能夠阻斷腫瘤的生長。經BCMab1單抗或BCMab1-Ra給藥的動物均沒有出現全身及局部的毒副作用。該研究顯示：BCMab1抗體及抗體毒素藥物BCMab1-Ra具有很強的抑制腫瘤生長的能力。今后研究人員可以通過這一靶點進行膀胱癌診斷試劑以及抗癌藥物的研發。

　　膀胱癌為泌尿系最常見的惡性腫瘤，發病率在美國被列為男性惡性腫瘤的第四位，在我國列為泌尿系腫瘤第一位。膀胱癌約95％來源于膀胱上皮，包括乳頭狀瘤、移行細胞癌、鱗狀細胞癌和腺癌。絕大多數為惡性，其中以移行細胞癌最常見，占80%以上。預后較差和極易復發是膀胱癌的最大特點，有效的治療將有賴于發現特異性高的膀胱癌腫瘤標志物。（

　　推薦的英文摘要：

　　Clinical Cancer Research doi: 10.1158/1078-0432.CCR-13-3397

　　BCMab1, A Monoclonal Antibody against Aberrantly Glycosylated Integrin α3β1, Has Potent Antitumor Activity of Bladder Cancer In Vivo

　　Chong Li, Zhao Yang, Ying Du, Haidong Tang, Jun Chen, Deqing Hu, and Zusen Fan

　　Abstract

　　Purpose: To identify a novel biomarker for bladder cancer targeting therapy.

　　Experimental Design: The human bladder cancer cell line T24 cells were used as immunogen to generate mouse monoclonal antibodies. We screened and identified a specific antibody BCMab1 against bladder cancer. We examined BCMab1 antigen expression in the patients with bladder cancer through immunohistochemical staining and investigated the BCMab1 antigen association with clinical severity. We detected the antitumor activity of BCMab1 antibody and investigated its therapeutic efficacy by subcutaneous and orthotopic bladder cancer models.

　　Results: We developed a new monoclonal antibody BCMab1 against bladder cancer that specifically recognized the aberrantly glycosylated Integrin α3β1 epitope on bladder cancer cells. Expression of the BCMab1 antigen was consistent with clinical severity and prognosis of bladder cancer. The glycosyltransferase GALNT1 could contribute to aberrant glycosylation of Integrin α3. The aberrant glycosylation of integrin α3-activated integrin signaling to initiate FAK activation. BCMab1 could block Integrin engagement to inhibit its signaling leading to cell-cycle arrest. In addition, BCMab1 enhanced FcγR-dependent antitumor activity in vivo.

　　Conclusions: BCMab1 antigen is a new biomarker for bladder cancer. BCMab1 antibody exhibited potent antitumor activity against bladder cancer in vivo.

　　膀胱癌的治療藥物有什么？膀胱癌的治療藥物可以選擇：草烏甲素口服溶液、消癌平片、金刺參九正合劑等藥物進行輔助治療的。

　　詳情請致電我們的客服垂詢：400-101-6868。如需購買草烏甲素口服溶液、消癌平片、金刺參九正合劑，可到臨近門店。廣州總店地址廣東省廣州市越秀區先烈南路23號之一A6-A7。門店電話：020-87613558, 020-37611352。

　　腫瘤科藥師溫馨提醒：膀胱刺激癥狀：尿頻、尿急、尿痛，約占10%，與廣泛分布的原位癌和浸潤性膀胱癌有關，尤其病變位于膀胱三角區時。故長期不能痊愈的膀胱炎應警惕膀胱癌可能，尤其是原位癌。

TAG：膀胱癌 腫瘤