Anti-Human VEGF x PD-L1 antibo

Palverafusp alfa （VEGF×PD-L1）是一种具有mAb-Trap结构的双特异性分子，靶向VEGF和PD-L1，用于治疗实体瘤。通过靶向VEGF和PD-L1，Palverafusp alfa能够激活T细胞肿瘤杀伤活性，同时抑制肿瘤血管生成和肿瘤生长。此外，Palverafusp alfa还可以通过Fc介导的ADCC/ADCP活性激活NK细胞和巨噬细胞。

Palverafusp alfa (VEGF×PD-L1)is a bispecific molecule with the mAb-Trap structure that targets VEGF and PD-L1 for the treatment of solid tumors. By targeting VEGF and PD-L1, Palverafusp alfa is able to activate T-cell tumor killing activities and simultaneously inhibit tumor angiogenesis and tumor growth. Moreover, Palverafusp alfa can also activate NK cells and macrophages through Fc-mediated ADCC/ADCP activities.

在过去的几年里，癌症免疫疗法一直伴随着有希望的结果。程序性细胞死亡蛋白1（Programmed Cell Death Protein 1，PD-1）通过调节T细胞活性、激活抗原特异性T细胞凋亡和抑制调节性T细胞凋亡，在抑制免疫应答和促进自身免疫耐受中发挥重要作用。程序性细胞死亡配体1（Programmed Cell Death Ligand 1，PD-L1）是一种跨膜蛋白，被认为是免疫应答的共抑制因子，它能与PD-1联合收割机结合，减少PD-1阳性细胞的增殖，抑制其细胞因子分泌，诱导细胞凋亡。PD-L1还在各种恶性肿瘤中发挥重要作用，它可以减弱宿主对肿瘤细胞的免疫反应。基于这些观点，PD-1/PD-L1轴负责癌症免疫逃逸，并对癌症治疗产生巨大影响。

PD-1（programmed cell death protein 1）是程序性死亡受体1，是活化的T细胞表达的免疫检查点受体，是一种重要的免疫抑制分子。PD-1通过向下调节免疫系统对人体细胞的反应，以及通过抑制T细胞炎症活动来调节免疫系统并促进自身耐受。这可以预防自身免疫疾病，但它也可以防止免疫系统杀死癌细胞。 PD-L1是PD-1的配体，PD-L1与免疫系统的抑制有关，可以传导抑制性的信号。肿瘤细胞也可以表达PD-L1，PD-1和PD-L1一旦结合便会向T细胞传递负向调控信号，导致T细胞无法识别癌细胞，肿瘤细胞从而实现“免疫逃逸”。 PD-1可表达在T细胞、B细胞等免疫细胞表面。不过在T细胞未活化时，几乎是不表达PD-1的，仅在T细胞活化之后，PD-1才表达在T细胞表面。 PD-L1除了会表达在肿瘤表面，参与免疫逃逸，还会在IFN-γ刺激下，表达在抗原提呈细胞（DC细胞、巨噬细胞等），以及血管内皮细胞的表面。

Cancer immunotherapy has been accompanied by promising results over the past few years. Programmed Cell Death Protein 1 (PD-1) plays a vital role in inhibiting immune responses and promoting self-tolerance through modulating the activity of T-cells, activating apoptosis of antigen-specific T cells and inhibiting apoptosis of regulatory T cells. Programmed Cell Death Ligand 1 (PD-L1) is a trans-membrane protein that is considered to be a co-inhibitory factor of the immune response, it can combine with PD-1 to reduce the proliferation of PD-1 positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 also plays an important role in various malignancies where it can attenuate the host immune response to tumor cells. Based on these perspectives, PD-1/PD-L1 axis is responsible for cancer immune escape and makes a huge effect on cancer therapy. This review is aimed to summarize the role of PD-1 and PD-L1 in cancer, looking forward to improve the therapy of cancer.