Jung Susanne, Heitmann Jonas, Pflügler Martin, Jung Gundram, Rausch Steffen, Salih Helmut
KKE Translationale Immunologie, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland.
Urologie. 2025 Apr 2. doi: 10.1007/s00120-025-02574-w.
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.
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，治疗选择就很有限。尽管付出了巨大努力，但在其他癌症实体中彻底改变肿瘤治疗方式的基于T细胞的免疫治疗策略，几乎尚未确立用于PC的治疗。这包括免疫检查点抑制，其通常增强T细胞免疫，但在PC中未能实现广泛活性，以及嵌合抗原受体T（CART）细胞和双特异性抗体（bsAb），它们特异性地动员T细胞对抗肿瘤细胞。与CART细胞相比，bsAb具有随时可用的“现成”试剂的优势。目前有几种双特异性构建体正在针对PC进行研发。虽然一些因严重副作用或抗药抗体的产生而停止研发，但其他一些已取得了有希望的结果。其中特别包括针对前列腺六跨膜上皮抗原1（STEAP1）和前列腺特异性膜抗原（PSMA）的双特异性抗体，目前正在转移性疾病患者和生化复发患者中进行评估。本文讨论了不同构建体的潜在概念、临床研发现状及未来前景。
