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实体瘤的放射免疫疗法:聚焦于Glypican-1作为放射免疫疗法靶点

Radioimmunotherapy for solid tumors: spotlight on Glypican-1 as a radioimmunotherapy target.

作者信息

Sabanathan Dhanusha, Lund Maria E, Campbell Douglas H, Walsh Bradley J, Gurney Howard

机构信息

Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.

GlyTherix Ltd, Sydney, NSW, Australia.

出版信息

Ther Adv Med Oncol. 2021 Oct 8;13:17588359211022918. doi: 10.1177/17588359211022918. eCollection 2021.

Abstract

Radioimmunotherapy (i.e., the use of radiolabeled tumor targeting antibodies) is an emerging approach for the diagnosis, therapy, and monitoring of solid tumors. Often using paired agents, each targeting the same tumor molecule, but labelled with an imaging or therapeutic isotope, radioimmunotherapy has achieved promising clinical results in relatively radio-resistant solid tumors such as prostate. Several approaches to optimize therapeutic efficacy, such as dose fractionation and personalized dosimetry, have seen clinical success. The clinical use and optimization of a radioimmunotherapy approach is, in part, influenced by the targeted tumor antigen, several of which have been proposed for different solid tumors. Glypican-1 (GPC-1) is a heparan sulfate proteoglycan that is expressed in a variety of solid tumors, but whose expression is restricted in normal adult tissue. Here, we discuss the preclinical and clinical evidence for the potential of GPC-1 as a radioimmunotherapy target. We describe the current treatment paradigm for several solid tumors expressing GPC-1 and suggest the potential clinical utility of a GPC-1 directed radioimmunotherapy for these tumors.

摘要

放射免疫疗法(即使用放射性标记的肿瘤靶向抗体)是一种用于实体瘤诊断、治疗和监测的新兴方法。放射免疫疗法通常使用成对的试剂,每种试剂靶向相同的肿瘤分子,但标记有成像或治疗同位素,在前列腺等相对抗辐射的实体瘤中已取得了有前景的临床结果。几种优化治疗效果的方法,如剂量分割和个性化剂量测定,已取得临床成功。放射免疫疗法方法的临床应用和优化部分受靶向肿瘤抗原的影响,针对不同实体瘤已提出了几种肿瘤抗原。磷脂酰肌醇蛋白聚糖-1(GPC-1)是一种硫酸乙酰肝素蛋白聚糖,在多种实体瘤中表达,但在正常成人组织中表达受限。在此,我们讨论GPC-1作为放射免疫疗法靶点潜力的临床前和临床证据。我们描述了几种表达GPC-1的实体瘤的当前治疗模式,并提出GPC-1导向的放射免疫疗法对这些肿瘤的潜在临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4f7/8504276/fb08b8d183d8/10.1177_17588359211022918-fig1.jpg

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