Reschke Robin, Enk Alexander H, Hassel Jessica C
Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
German Cancer Consortium (DKTK), Core Center Heidelberg, 69120 Heidelberg, Germany.
Pharmaceutics. 2024 Aug 6;16(8):1046. doi: 10.3390/pharmaceutics16081046.
Uveal melanoma represents a rare and aggressive subtype of melanoma with limited treatment options and poor prognosis, especially in the metastatic setting. Tebentafusp, a bispecific fusion protein, offers a promising therapeutic approach by targeting gp100, an antigen highly expressed in uveal melanoma cells, and redirecting T cell-mediated cytotoxicity towards tumor cells. This review provides an overview of the preclinical and clinical data on tebentafusp in the management of metastatic uveal melanoma. We summarize the mechanism of action, clinical efficacy, safety profile, and ongoing research efforts surrounding this innovative immunotherapy. Preclinical studies have demonstrated the ability of tebentafusp to induce potent and specific anti-tumor immune responses against gp100-expressing uveal melanoma cells. Clinical trials have shown encouraging results, with tebentafusp exhibiting meaningful clinical activity in a subset of patients with metastatic uveal melanoma. Importantly, tebentafusp has also demonstrated a manageable safety profile. By specifically targeting tumor cells expressing gp100, tebentafusp offers a promising therapeutic avenue for individuals with metastatic uveal melanoma, meeting a significant clinical need in this context. Continued clinical trials will provide additional insights into the impact of tebentafusp on treatment-resistant metastatic cutaneous melanoma. Furthermore, we are exploring the potential of T cell engagers directed against the cancer testis antigen PRAME, which could have widespread utility in the treatment of cutaneous melanoma as well as other PRAME-expressing malignancies.
葡萄膜黑色素瘤是黑色素瘤的一种罕见且侵袭性强的亚型，治疗选择有限且预后较差，尤其是在转移情况下。替贝福单抗是一种双特异性融合蛋白，通过靶向葡萄膜黑色素瘤细胞中高表达的抗原gp100，并将T细胞介导的细胞毒性重定向至肿瘤细胞，提供了一种有前景的治疗方法。本综述概述了替贝福单抗治疗转移性葡萄膜黑色素瘤的临床前和临床数据。我们总结了这种创新免疫疗法的作用机制、临床疗效、安全性概况以及正在进行的研究工作。临床前研究已证明替贝福单抗能够诱导针对表达gp100的葡萄膜黑色素瘤细胞产生强效且特异性的抗肿瘤免疫反应。临床试验显示了令人鼓舞的结果，替贝福单抗在一部分转移性葡萄膜黑色素瘤患者中表现出有意义的临床活性。重要的是，替贝福单抗也已证明其安全性可控。通过特异性靶向表达gp100的肿瘤细胞，替贝福单抗为转移性葡萄膜黑色素瘤患者提供了一条有前景的治疗途径，满足了这一背景下的重大临床需求。持续的临床试验将提供关于替贝福单抗对难治性转移性皮肤黑色素瘤影响的更多见解。此外，我们正在探索针对癌睾丸抗原PRAME的T细胞衔接子的潜力，其在皮肤黑色素瘤以及其他表达PRAME的恶性肿瘤治疗中可能具有广泛应用。
