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PA007164.r2b: Syd Labs体内实验级重组抗小鼠PD-L1单克隆抗体（克隆号10F.9G2.1），大鼠IgG2b Kappa（In Vivo Grade Recombinant Anti-mouse PD-L1 Monoclonal Antibody (Clone 10F.9G2.1), Rat IgG2b Kappa）

大鼠抗小鼠 PD-L1 单克隆抗体 10F.9G2（大鼠 IgG2b Kappa）可与小鼠 PD-L1 蛋白（程序化死亡受体配体-1、B7-H1 或 CD274）发生特异性反应，PD-L1 属于免疫球蛋白超家族的 B7 家族成员。PD-1 拥有两个配体，即 PD-L1 和 PD-L2。研究表明，在小鼠黑色素瘤模型中，通过使用抗小鼠 PD-1 和抗小鼠 PD-L1 抗体阻断 PD-L1 蛋白与其受体 PD-1 蛋白之间的相互作用，可一过性抑制肿瘤生长。10F.9G2 单克隆抗体能够阻断小鼠 PD-L1 蛋白与小鼠 PD-1 蛋白的结合。

我们的重组 10F.9G2 抗体包含了大鼠抗小鼠 PD-L1 单克隆抗体（杂交瘤克隆号：10F.9G2）的部分（可变区）或完整的氨基酸序列。

抗小鼠PD-L1单抗（10F.9G2）部分参考文献:

1. The Antitumor Activity of Combinations of Cytotoxic Chemotherapy and Immune Checkpoint Inhibitors Is Model-Dependent.

Grasselly, et al. Front Immunol. 2018 Oct 9;9:2100. PMID: 30356816

“Immune checkpoint inhibitors (ICI), such as anti-PD-1 (Programmed cell death 1) or anti-PD-L1 (Programmed death-ligand 1) antibodies, are among the most important recent breakthroughs in oncology. …The PD-1/PD-L1 axis induces an inhibitory signal in T cells, and PD-1/PD-L1 pathway blockade restores T cell function resulting in increased proliferation and cytotoxic activity, subsequently improving anti-tumor immune response. …For this reason, it is crucial to develop new therapeutic approaches to enhance the therapeutic effects of PD-1/PD-L1 blockade, and to avoid resistance phenomena. …We performed an exploratory study of various combination regimens of chemotherapies with immune checkpoint blockers anti-PD-1 and anti-PD-L1, in several murine syngeneic preclinical models. …Remarkably the MVAC regimen had a different impact when combined with anti-PD-L1 Mab in the MB49 bladder model and in the MBT2 bladder model, supporting an influence of the model on the sensitivity to combination regimens.”

2. Highly pathological influenza A virus infection is associated with increased expression of PD-1 by functionally compromised virus-specific CD8+ T cells.

Rutigliano, et al. J Virol. 2014 Feb;88(3):1636-51. PMID: 24257598

“High-pathological infection was associated with increased PD-1 expression on influenza virus-specific CD8+ T cells, and blockade of PD-L1 in vivo led to reduced virus titers and increased CD8+ T cell numbers in high- but not low-pathological infection, though T cell functionality was not restored. …Blockade of PD-L1, one of two known ligands for PD-1, restores CD8+ T cell functionality and wholly improves the response to chronic lymphocytic choriomeningitis virus (LCMV) infection. …This expression was reversed by anti-PD-L1 treatment. Another study used a self-antigen system to show that PD-1 was expressed early on hemagglutinin-specific CD8+ T cells, and blockade of PD-L1 at the time of self-antigen encounter led to development of functional CD8+ T cells. …PD-L1 expression is also elevated on CD45+ MHCII? cells during infection with 104 EID50 of PR8. Interestingly, we found that at day 7, coexpression of PD-L1 and PD-L2 on MHCII+ CD45+ cells was spectacularly increased in x31-infected mice compared to PR8-infected mice. …Treatment with anti-PD-L1 antibody alone has been shown to rescue PD-1-induced exhaustion.”

3. Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8+ T cells and efficiently reduces chronic retroviral loads.

Dietze, et al. PLoS Pathog. 2013;9(12):e1003798. PMID: 24339778

“The PD-1 receptor is a negative regulator of T cell proliferation and activation and is known to mediate suppressive functions when bound to its ligands PD-L1 or PD-L2. …Another group of animals was injected with monoclonal antibodies against PD-L1 and Tim-3 to block inhibitory receptor signaling on CD8+ T cells. …A 4-fold expansion of CD43+ CD8+ T cells was also found in mice treated with ?-PD-L1 and ?-TIM-3 but it was significantly lower than in the group of Treg depleted mice. …This suggested that ?-PD-L1 and ?-TIM-3 treatment might be more potent than ablation of Tregs in diminishing chronic virus loads. …However, this was only reflected in augmented FV-specific target cell killing when Treg depleted mice were compared to the animals receiving DT plus ?-PD-L1 and ?-TIM-3.”

4. The CTLA-4 and PD-1/PD-L1 inhibitory pathways independently regulate host resistance to Plasmodium-induced acute immune pathology.

Hafalla, et al. PLoS Pathog. 2012 Feb;8(2):e1002504. PMID: 22319445

“Accumulating data suggest that PD-1/PD-L1 signalling, and in some cases CTLA-4 signalling, is implicated in the T cell exhaustion that is seen in many chronic infections. …In vitro blockade of PD-1/PD-L1 pathway significantly increases CD8+ and CD4+ T cell function during HIV infection. …In vitro blockade of PD-1/PD-L1 and to a lesser extent PD-1/PD-L2 resulted in reversal of immune dysfunction in HCV. …Limited data are available for the PD-1/PD-L2 pathway during acute infections: PD-1/PD-L2 but not PD-1/PD-L1 blockade favours trypanosomatid growth in macrophages [35] and PD-L2 blockade enhances Th2 responses during Nippostrongylus infection [36]. …Thus, the CTLA-4 and PD-1/PD-L1 pathways seem to function very efficiently in BALB/c mice, maintaining the balance between immunity and immune pathology during the critical early stage of infection.”

5. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model.

Zhang, et al. Blood. 2009 Aug 20;114(8):1545-52. PMID: 19417208

“In normal hosts, PD-1/PD-L1 interactions contribute to the maintenance of peripheral tolerance to self-antigens. …Conversely, PD-L1 mRNA is broadly expressed in tissues,7,8 and protein expression has been detected on many tumor cell types,15 and can be further induced by exposure to interferon (IFN)-?. Mounting evidence suggests that PD-L1 expression on solid tumor cells is capable of dampening antitumor T-cell responses. …Chen et al measured PD-L1 expression on bone marrow samples from patients with acute myeloid leukemia (AML) and found increasing levels upon disease progression, which was an independent negative prognostic factor for French-American-British type M5 AML. …To investigate if the PD-1/PD-L1 pathway promotes immune escape in a murine AML model, C57BL/6 or PD-1?/? mice were challenged intravenously (IV) with a highly lethal, syngeneic AML cell line, C1498, transduced to express green fluorescent protein (C1498.GFP) to allow monitoring of tumor burden. …These results confirm that the PD-1/PD-L1 pathway inhibits effective antitumor immune responses against murine AML, and support a rationale for clinical trials examining anti?PD-1 antibodies in patients with hematologic malignancies.”

关于重组抗小鼠 PD-L1 抗体（克隆号：10F.9G2）的常见问题解答 (FAQ)

问：你们生产具有 Fc 静默（Fc-silenced）功能的 10F.9G2 抗体吗？
答：当然，我们提供多种重组 Fc 静默型 10F.9G2 抗体，例如小鼠 IgG2c-LALAPG、小鼠 IgG2a-LALAPG 和小鼠 IgG1-D265A。我们还提供定制重组抗体生产服务，以制备其他工程化版本的 10F.9G2 抗体。

问：PA007164.r2b 和 PA007164.m2cLA 之间有什么区别？
答：PA007164.r2b 是在 CHO 细胞（或按需在 HEK293 细胞）中生产的重组抗小鼠 PD-L1 单克隆抗体（大鼠 IgG2b Kappa，克隆号 10F.9G2.1）。它具有与杂交瘤克隆 10F.9G2 的大鼠抗小鼠 PD-L1 单克隆抗体相同的高度可变区和恒定区序列。大鼠抗体在小鼠体内可能会引起高免疫原性；通常情况下，应当使用至少带有小鼠抗体恒定区的重组抗体来替代大鼠抗体恒定区。而 PA007164.m2cLA 是重组抗小鼠 PD-L1 抗体（克隆号 10F.9G2.1），其恒定区改造为小鼠 IgG2c-LALAPG Kappa。

了解更多抗小鼠PD-L1单抗（10F.9G2）参考文献，请查看：参考文献