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The Role of αvβ6 Integrin Binding Molecules in the Diagnosis and Treatment of Cancer
Current Organic Chemistry ( IF 1.7 ) Pub Date : 2020-10-31 , DOI: 10.2174/1385272824999200528124936
Mauricio Urquiza 1 , Valentina Guevara 1 , Erika Diaz-Sana 1 , Felipe Mora 1
Affiliation  

Peptidic and non-peptidic αvβ6 integrin-binding molecules have been used in the clinic for detection and treatment of tumors expressing αvβ6 integrin, because this protein is expressed in malignant epithelial cells of the oral cavity, pancreas, breast, ovary, colon and stomach carcinomas but it is not expressed in healthy adult tissue except during wound healing and inflammation. This review focuses on the landscape of αvβ6 integrinbinding molecules and their use in cancer treatment and detection, and discusses recent designs for tumor detection, treatment, and immunotherapy. In the last ten years, several reviews about the αvβ6 integrin have been published but no one assessed the landscape of the αvβ6 integrin-binding molecules and their role in cancer detection and treatment. Firstly, this review describes the role of the αvβ6 integrin in normal tissues, how the expression of this protein is correlated with cancer severity and its role in cancer development. Taking into account the potential of αvβ6 integrin-binding molecules in detection and treatment of specific tumors, special attention is given to several high-affinity αvβ6 integrin-binding peptides used for tumor imaging; particularly, the αvβ6-binding peptide NAVPNLRGDLQVLAQKVART [A20FMDV2], derived from the foot and mouth disease virus. This peptide labeled with either 18F, 111In or with 68Ga has been used for PET imaging of αvβ6 integrin-positive tumors. Moreover, αvβ6 integrin-binding peptides have been used for photoacoustic and fluorescence imaging and could potentially be used in clinical application in cancer diagnosis and intraoperative imaging of αvβ6-integrin positive tumors. Additionally, non-peptidic αvβ6-binding molecules have been designed and used in the clinic for the detection and treatment of αvβ6-expressing tumors. Anti-αvβ6 integrin antibodies are another useful tool for selective identification and treatment of αvβ6 (+) tumors. The utility of these αvβ6 integrin-binding molecules as a tool for tumor detection and treatment is discussed, considering specificity, sensitivity and serum stability. Another use of the αvβ6 integrin-binding peptides is to modify the Ad5 cell tropism for inducing oncolytic activity of αvβ6-integrin positive tumor cells by expressing A20FMDV2 peptide within the fiber knob protein (Ad5NULL-A20). The newly designed oncolytic Ad5NULL-A20 virotherapy is promising for local and systemic targeting of αvβ6-overexpressing cancers. Finally, new evidence has emerged, indicating that chimeric antigen receptor (CAR) containing the αvβ6 integrin- binding peptide on top of CD28+CD3 endodomain displays a potent therapeutic activity in a diverse repertoire of solid tumor models.



中文翻译:

αvβ6整合素结合分子在癌症诊断和治疗中的作用

肽和非肽αvβ6整联蛋白结合分子已在临床上用于检测和治疗表达αvβ6整联蛋白的肿瘤,因为该蛋白在口腔,胰腺,乳腺癌,乳腺癌,卵巢癌,结肠癌和胃癌的恶性上皮细胞中表达但除了伤口愈合和发炎外,它不在健康的成人组织中表达。本文综述了αvβ6整联蛋白结合分子的概况及其在癌症治疗和检测中的用途,并讨论了肿瘤检测,治疗和免疫疗法的最新设计。在过去的十年中,已经发表了几篇有关αvβ6整联蛋白的综述,但是没有人评估αvβ6整联蛋白结合分子的概况及其在癌症检测和治疗中的作用。首先,这篇综述描述了αvβ6整联蛋白在正常组织中的作用,该蛋白的表达与癌症严重程度及其在癌症发展中的作用如何相关。考虑到αvβ6整联蛋白结合分子在检测和治疗特定肿瘤中的潜力,特别关注了几种用于肿瘤成像的高亲和力αvβ6整联蛋白结合肽。特别是源自口蹄疫病毒的αvβ6结合肽NAVPNLRGDLQVLAQKVART [A20FMDV2]。用18F,111In或68Ga标记的这种肽已用于αvβ6整联蛋白阳性肿瘤的PET成像。此外,αvβ6整联蛋白结合肽已用于光声和荧光成像,并有可能用于临床诊断αvβ6-整联蛋白阳性肿瘤的诊断和术中成像。另外,已经设计了非肽αvβ6结合分子并将其用于临床中用于表达αvβ6的肿瘤的检测和治疗。抗αvβ6整联蛋白抗体是用于选择性鉴定和治疗αvβ6(+)肿瘤的另一种有用工具。考虑到特异性,敏感性和血清稳定性,讨论了这些αvβ6整联蛋白结合分子作为肿瘤检测和治疗工具的实用性。αvβ6整联蛋白结合肽的另一个用途是通过在纤维结蛋白(Ad5NULL-A20)中表达A20FMDV2肽来修饰Ad5细胞向性,以诱导αvβ6-整联蛋白阳性肿瘤细胞的溶瘤活性。新设计的溶瘤Ad5NULL-A20病毒疗法有望用于局部和全身性靶向过表达αvβ6的癌症。最后,出现了新的证据,表明在CD28 + CD3内结构域顶部包含αvβ6整联蛋白结合肽的嵌合抗原受体(CAR)在多种实体瘤模型库中均显示出强大的治疗活性。

更新日期:2020-12-12
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