抗免疫检查点分子的抗体通过抑制PD-1和PD-L1的结合来恢复T细胞功能，在多种人类癌症中已显示出治疗效果。然而，迄今为止，没有报道能识别猫PD-1或PD-L1的单克隆抗体，关于免疫检查点分子的表达及其作为治疗靶点的潜力仍存在许多未知。本研究开发出抗猫PD-1单克隆抗体(1A1-2)，并发现先前在我们实验室开发的抗犬PD-L1单克隆抗体(G11-6)与猫PD-L1交叉反应。两种抗体都可以体外抑制猫PD-1和猫PD-L1之间的相互作用。这些抑制性单克隆抗体增强了激活的猫外周血淋巴细胞(PBLs)中干扰素-γ (IFN-γ)的产生。此外，为了在猫中实现临床应用，我们通过将1A1-2克隆的可变区域与猫IgG1的恒定区域融合而生成了一个小鼠-猫嵌合mAb (ch-1A1-2)。Ch-1A1-2同样增强了激活的猫PBLs中的IFN-γ产生。从本研究中，1A1-2是第一个具有抑制猫PD-1和PD-L1相互作用能力的抗猫PD-1单克隆抗体，而嵌合抗体ch-1A1-2将成为治疗猫肿瘤的有益治疗抗体。©2023.作者。

Antibodies against immune checkpoint molecules restore T-cell function by inhibiting the binding of PD-1 and PD-L1 and have been shown to exert therapeutic effects in various human cancers. However, to date, no monoclonal antibody that recognizes feline PD-1 or PD-L1 has been reported, and there are many unknowns regarding the expression of immune checkpoint molecules and their potential as therapeutic targets in cats. Here we developed anti-feline PD-1 monoclonal antibody (1A1-2), and found that the monoclonal antibody against anti-canine PD-L1 (G11-6), which was previously developed in our laboratory, cross-reacted with feline PD-L1. Both antibodies inhibited the interaction of feline PD-1 and feline PD-L1 in vitro. These inhibitory monoclonal antibodies augmented the interferon-gamma (IFN-γ) production in activated feline peripheral blood lymphocytes (PBLs). Furthermore, for clinical application in cats, we generated a mouse-feline chimeric mAb by fusing the variable region of clone 1A1-2 with the constant region of feline IgG1 (ch-1A1-2). Ch-1A1-2 also augmented the IFN-γ production in activated feline PBLs. From this study, 1A1-2 is first anti-feline PD-1 monoclonal antibody with the ability to inhibit the interaction of feline PD-1 and PD-L1, and the chimeric antibody, ch-1A1-2 will be a beneficial therapeutic antibody for feline tumors.© 2023. The Author(s).