Anti-Human PD1x ICOS antibody

Izuralimab 是一种双特异性IgG1抗体，靶向诱导 T 细胞共刺激因子 (ICOS/CD278) 和PD-1。一种人源化、Fc工程化双特异性单克隆抗体，其针对人负性免疫调节检查点受体、程序性细胞死亡蛋白1（PD-1; PCD-1; CD 279）和诱导型T细胞共刺激因子（ICOS; CD 278），具有潜在的免疫调节和抑制活性。给药后，izuralimab靶向并结合某些T细胞（包括肿瘤浸润淋巴细胞（TIL））上表达的PD-1和ICOS。这阻止了PD-1通过其配体，程序性细胞死亡-1配体1（PD-L1）和PD-1配体2（PD-L2）的活化，并刺激ICOS介导的信号传导，其促进T细胞的活化并增强T细胞介导的针对肿瘤细胞的免疫应答。联合PD-1阻断和ICOS刺激可能比单独靶向每种受体更能增强T细胞活化和增殖。工程化的Fc结构域增加了抗体的稳定性和半衰期。

Izuralimab is a bispecific IgG1 antibody that targets both the inducible T-cell costimulator (ICOS/CD278) and PD-1。A humanized, Fc-engineered bispecific monoclonal antibody directed against both the human negative immunoregulatory checkpoint receptor, programmed cell death protein 1 (PD-1; PCD-1; CD279), and inducible T-cell co-stimulator (ICOS; CD278), with potential immunomodulating and antineoplastic activities. Upon administration, izuralimab targets and binds to both PD-1 and ICOS expressed on certain T cells, including tumor-infiltrating lymphocytes (TILs). This prevents the activation of PD-1 by its ligands, programmed cell death-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2), and stimulates ICOS-mediated signaling, which promotes the activation of T cells and enhances T-cell-mediated immune responses against tumor cells. Combined PD-1 blockade and ICOS stimulation may enhance T-cell activation and proliferation more than targeting each receptor individually. The engineered Fc domain increases the stability and half-life of the antibody。

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.