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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

肿瘤穿透肽功能性腱糖蛋白C抗体靶向胶质母细胞瘤。

卷 21, 期 1, 2021

发表于: 01 October, 2020

页: [70 - 79] 页: 10

弟呕挨: 10.2174/1568009620666201001112749

open access plus

摘要

背景：与临床级肿瘤穿透性iRGD肽结合，是一种广泛应用的改善肿瘤归巢、外渗和肿瘤药物和肿瘤显像剂渗透的策略。实体瘤中细胞外基质分子Tenascin-C（TNC-C）的C结构域被上调，并且代表了基于临床级基于单链抗体的肿瘤递送药物和显像剂的诱人靶标。 目的：研究iRGD肽与重组抗TNC-C单链抗体克隆G11的C端基因融合对系统性肿瘤归巢和外渗的影响。 方法：采用酶联免疫吸附法研究亲本和iRGD融合的抗TNC-C单链抗体与腱糖蛋白C的C结构域和αVβ3整联蛋白的相互作用。为了进行全身归巢研究，在U87-MG胶质母细胞瘤异种移植小鼠中施用了荧光素标记的ScFV G11-iRGD和ScFV G11抗体，并通过共聚焦成像对组织切片进行了共聚焦成像研究其生物分布，所述组织切片被血管标记和腱生蛋白C免疫反应性染色。 结果：在无细胞系统中，iRGD与ScFV G11融合赋予了抗体强大的结合αVβ3整联蛋白的能力。 ScFV G11-iRGD的荧光素标记不影响其靶结合活性。在U87-MG小鼠中，iRGD与ScFV G11抗体的融合改善了其归巢于肿瘤血管，外渗和肿瘤实质的渗透。 结论：iRGD肿瘤穿透肽与非内在亲和力靶向配体的基因融合可改善其肿瘤嗜性和实质渗透，从而将成像和治疗剂更有效地递送至实体瘤病变中。

关键词: 腱生蛋白C，细胞外基质，iRGD，单链抗体，肿瘤穿透肽，胶质母细胞瘤。

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