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用荧光团偶联的粘蛋白4(MUC4)抗体靶向人类胰腺癌:原位细胞系小鼠模型的初步表征

Targeting Human Pancreatic Cancer with a Fluorophore-Conjugated Mucin 4 (MUC4) Antibody: Initial Characterization in Orthotopic Cell Line Mouse Models.

作者信息

Jaiswal Sunidhi, Cox Kristin E, Amirfakhri Siamak, Din Parast Saleh Aylin, Kobayashi Keita, Lwin Thinzar M, Talib Sumbal, Aithal Abhijit, Mallya Kavita, Jain Maneesh, Mohs Aaron M, Hoffman Robert M, Batra Surinder K, Bouvet Michael

机构信息

Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA.

VA San Diego Healthcare System, La Jolla, CA 92161, USA.

出版信息

J Clin Med. 2024 Oct 18;13(20):6211. doi: 10.3390/jcm13206211.

Abstract

Pancreatic cancer is the third leading cause of death related to cancer. The only possible cure presently is complete surgical resection; however, this is limited by difficulty in clearly defining tumor margins. Enhancement of the visualization of pancreatic ductal adenocarcinoma (PDAC) tumor margins using near-infrared dye-conjugated tumor-specific antibodies was pioneered by using anti-CEA, anti-CA19.9, and anti-MUC5AC in orthotopic mouse models of pancreatic cancer. Recently, an antibody to Mucin 4 (MUC4) conjugated to a fluorescent probe has shown promise in targeting colon tumors in orthotopic mouse models. In the present study, we targeted pancreatic cancer using an anti-MUC4 antibody conjugated to IRDye800 (anti-MUC4-IR800) in orthotopic mouse models. Two pancreatic cancer human cell lines were used, SW1990 and CD18/HPAF. Anti-MUC4-IR800 targeted the two pancreatic cancer cell line tumors in orthotopic mouse models with high tumor-to-pancreas ratios and high tumor-to-liver ratios, with greater targeting seen in SW1990. The present results suggest anti-MUC4-IR800's potential to be used in fluorescence-guided surgical resection of pancreatic cancer.

摘要

胰腺癌是癌症相关死亡的第三大主要原因。目前唯一可能的治愈方法是完全手术切除;然而,这受到难以清晰界定肿瘤边界的限制。在胰腺癌原位小鼠模型中,通过使用抗癌胚抗原(CEA)、抗糖类抗原19.9(CA19.9)和抗粘蛋白5AC(MUC5AC),率先实现了使用近红外染料偶联的肿瘤特异性抗体增强胰腺导管腺癌(PDAC)肿瘤边界的可视化。最近,一种与荧光探针偶联的粘蛋白4(MUC4)抗体在原位小鼠模型中靶向结肠肿瘤方面显示出前景。在本研究中,我们在原位小鼠模型中使用与IRDye800偶联的抗MUC4抗体(抗MUC4-IR800)靶向胰腺癌。使用了两种胰腺癌人类细胞系,SW1990和CD18/HPAF。抗MUC4-IR800在原位小鼠模型中靶向两种胰腺癌细胞系肿瘤,肿瘤与胰腺的比例以及肿瘤与肝脏的比例都很高,在SW1990中观察到更强的靶向作用。目前的结果表明抗MUC-IR800有潜力用于胰腺癌的荧光引导手术切除。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4212/11508345/e9b6a811cbba/jcm-13-06211-g001.jpg

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