双特异性抗体在前列腺癌治疗中的应用

IF 0.5 4区 医学 Q4 UROLOGY & NEPHROLOGY
Susanne Jung, Jonas Heitmann, Martin Pflügler, Gundram Jung, Steffen Rausch, Helmut Salih
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引用次数: 0

摘要

前列腺癌(PC)是男性中第二常见的癌症。一旦雄激素剥夺疗法失败,治疗选择就有限了。尽管付出了巨大的努力,但几乎没有任何基于T细胞的免疫治疗策略已经彻底改变了其他癌症实体的肿瘤治疗,但尚未建立用于治疗PC。这包括免疫检查点抑制,它通常增强T细胞免疫,但在PC中无法实现广泛的活性,以及嵌合抗原受体T (CART)细胞和双特异性抗体(bsAbs),它们特异性地动员T细胞对抗肿瘤细胞。与CART细胞相比,bsab具有易于获得的“现成”试剂的优势。目前正在为PC开发几个双特异性结构。虽然一些药物的开发由于严重的副作用或抗药物抗体的开发而停止,但其他药物已经产生了有希望的结果。其中特别包括针对前列腺1六跨膜上皮抗原(STEAP1)和前列腺特异性膜抗原(PSMA)的bsab,目前正在对转移性疾病和生化复发患者进行评估。讨论了不同结构的概念、临床发展的现状和未来的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Bispecific antibodies in prostate cancer therapy].

Prostate cancer (PC) is the second most common cancer in men. As soon as androgen deprivation therapy fails, treatment options are limited. Despite intense efforts, hardly any of the T cell-based immunotherapeutic strategies that have revolutionized oncological treatment in other cancer entities are yet established for the treatment of PC. This includes immune checkpoint inhibition, which generally reinforces T cell-immunity but failed to achieve broad activity in PC, as well as chimeric antigen receptor T (CART) cells and bispecific antibodies (bsAbs), which specifically mobilize T cells against tumor cells. Compared to CART cells, bsAbs have the advantage of being readily available "off-the-shelf" reagents. Currently several bispecific constructs are in development for PC. While development of some was discontinued due to substantial side effects or development of anti-drug antibodies, others have yielded promising results. These include in particular bsAbs directed against six-transmembrane epithelial antigen of the prostate 1 (STEAP1) and prostate-specific membrane antigen (PSMA), which are currently being evaluated in both patients with metastasized disease and biochemical relapse. The concepts underlying the different constructs, the current status of clinical development, and future perspectives are discussed.

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来源期刊
Urologie
Urologie UROLOGY & NEPHROLOGY-
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