程序性细胞死亡蛋白 1 (PD-1) 和细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 抗体的组合具有增强临床疗效的潜力。我们描述了 Z15-0 的开发和抗肿瘤活性，Z15-0 是一种同时靶向 PD-1 和 CTLA-4 途径的双特异性纳米抗体。我们设计并优化了编码Z15-0的mRNA序列，简称为Z15-0-2，通过一系列体外和体内实验，我们确定优化后的Z15-0-2 mRNA序列显着增加了Z15-0-2的表达。双特异性纳米抗体。与对照组相比，对荷瘤小鼠施用 Z15-0-2 mRNA 可以更好地抑制肿瘤生长。总的来说，我们引入了一种新型双特异性纳米抗体，并对其进行了重新设计以增强 mRNA 的表达，代表了一种新的药物开发范例。© 2024。作者。

The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.© 2024. The Author(s).