文献

PA007162.m1DA: Syd Labs 重组抗小鼠PD-1单抗（RMP1-14.1）,（In Vivo Grade Recombinant Anti-mouse PD-1 Monoclonal Antibody , Mouse IgG1-D265A Kappa）

大鼠抗小鼠 PD-1 单克隆抗体（克隆号：RMP1-14.1，Rat IgG2a kappa）可与小鼠 PD-1 蛋白（CD279 或程序性死亡受体 1）发生特异性反应。该蛋白由小鼠pdcd1基因编码，属于免疫球蛋白超家族（Ig superfamily）中的 CD28 家族成员。PD-1 拥有 PD-L1 和 PD-L2 两个配体，二者均属于 B7 家族。研究表明，在黑色素瘤和结肠癌的小鼠模型中，通过抗小鼠 PD-1 抗体治疗以及抗小鼠 PD-L1 抗体干预来阻断 PD-L1 蛋白与其受体 PD-1 蛋白之间的相互作用，可使肿瘤生长受到暂时的抑制。在体内检查点阻断实验中，RMP1-14.1 阻断型抗体能有效阻断小鼠 PD-L1 蛋白与小鼠 PD-L2 蛋白向小鼠 PD-1 蛋白的相互结合。

我们的重组 RMP1-14.1 抗体采用了源自原始大鼠杂交瘤（克隆号：RMP1-14）可变区的 100% 精确氨基酸序列进行基因工程重组。该体内级（In Vivo Grade）重组抗小鼠 PD-1 抗体采用先进的哺乳动物细胞表达，具备卓越的批间一致性，结合亲和力低于 2 nM，纯度大于 95%。产品提供多种灵活的格式选择，包括经典的 Rat IgG2a 以及 Fc 沉默型 Mouse IgG2c LALAPG（L234A/L235A/P329G）平台；采用低内毒素（< 1.0 EU/mg）、不含叠氮化物（Azide-free）的配方设计，可彻底消除非特异性细胞激活，是免疫组化（IHC）、流式细胞术（FC）、体外中和实验（In Vitro Neutralization）以及长期体内功能学实验的理想选择。

重组抗小鼠PD-1单抗（克隆号：RMP1-14.1）引用文献:

1、Spermidine potentiates anti-tumor immune responses and immunotherapy sensitivity in breast cancer

Xinyu Yang, et al. J Cancer 2025. doi: 10.7150/jca.113235

“In vivo spermidine supplementing experiment…To establish a subcutaneous tumor-bearing mouse model …… Docetaxel (Sanofi Mature IP) was administered intraperitoneally at 10 mg/kg one week after tumor inoculation in mice, followed by a single intraperitoneal injection of PD-1 antibody (SYD, PA007162) at a dosage of 10 mg/kg …… The Institutional Animal Care and Use Committee at Sun Yat-Sen University granted approval for animal experiments.”

2、PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior

Junli Zhao, et al. Neuron 2023. doi: 10.1016/j.neuron.2023.07.008

“Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Intraventricular administration of anti-mouse PD-1 monoclonal antibody (RMP1-14) potentiated learning and memory.”

3、PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration

Wenji Piao, et al. Nat Commun 2022. doi: 10.1038/s41467-022-29761-9

“Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs.”

4、Macrophages Impair TLR9 Agonist Antitumor Activity through Interacting with the Anti-PD-1 Antibody Fc Domain

Simone Camelliti, et al. Cancers (Basel) 2021. doi: 10.3390/cancers13164081

“We evaluated the contribution of macrophages to the effect of combinatorial immunotherapeutic treatments based on TLR9 stimulation (with CpG-ODNs) and PD-1 blockade in an ovarian cancer preclinical model. We observed a strong reduction in the antitumor efficacy of a TLR9 agonist upon anti-PD-1 antibody administration. Specifically, we found that TLR9-stimulated macrophages, through interacting with the fragment crystallizable (Fc) domain of the anti-PD-1 antibody, acquire an immunoregulatory phenotype leading to dampening of CpG-ODN antitumor effect.”

5、Prophylactic IL-23 blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy

Mingyi Ju, et al. J Immunother Cancer 2024. doi: 10.1136/jitc-2024-009144

“The onset of immune-related adverse events (irAEs) might serve as a clinical biomarker to predict a favorable therapeutic response to immune checkpoint inhibitors (ICIs). Moreover, in the PD-1 monotherapy cohort, patients with irAEs tended to achieve higher response rates than those lacking toxicity. Our findings fill the gap in the previous evidence that there was no correlation between irAEs and ICIs response in patients treated with anti-CTLA-4 therapy.”

6、Angiogenic inhibitor pre‐administration improves the therapeutic effects of immunotherapy

Ying Han, et al. Cancer Sci 2023. doi: 10.1111/cas.15783

“Angiogenic inhibitors combined with anti-PD-1 blockade has become a standard choice for multiple advanced malignancies. We demonstrated that pre-treatment with anti-angiogenic agents improves tumor vascular normalization. This optimal pre-administration schedule enhances the subsequent therapeutic efficacy of anti-mouse PD-1 antibody treatment in syngeneic models.”

7、Sources of inter-individual variability leading to significant changes in anti-PD-1 and anti-PD-L1 efficacy identified in mouse tumor models using a QSP framework

Chetan Kulkarni, et al. CPT Pharmacometrics Syst Pharmacol 2022. doi: 10.1002/psp4.12879

“Substantial inter-individual variability in response to immune checkpoint inhibition is observed clinically and in mouse models. We applied a quantitative systems pharmacology (QSP) model to investigate physiological drivers of variability. Our simulations identify critical parameters regulating anti-PD-1 efficacy and receptor occupancy profiles in murine syngeneic cohorts.”

8、Targeting PD-L2/RGMb overcomes microbiome-related immunotherapy resistance

Jong-Chan Park, et al. Nature 2023. doi: 10.1038/s41586-023-06103-x

“The gut microbiota significantly influences the response of tumors to immune checkpoint blockades. We identify that a subset of commensal microbes impairs anti-PD-1 therapeutic outcomes through distinct pathways. Concurrent blockade targeting the PD-L2/RGMb axis effectively overcomes this resistance and rescues anti-PD-1 treatment efficacy.”

9、Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo

Stephen J. Price, et al. Nat Biotechnol 2018. doi: 10.1038/nbt.4194

“Combining CAR-T cells with immune checkpoint inhibitors represents an attractive strategy to counter immunosuppressive environments. We engineered CAR-T cells to locally secrete an anti-PD-1 single-chain variable fragment (scFv). This localized action achieved superior therapeutic antitumor clearance compared to systemic combination with standard anti-PD-1 antibodies.”

10、Antibody-mediated depletion of programmed death 1-positive (PD-1+) cells

Takahiro Shimizu, et al. Immunology 2023. doi: 10.1111/imm.13702

“Anti-PD-1 antibodies are typically used to block inhibitory signals in dysfunctional T cells. Here, we developed an alternative strategy focused on eliminating PD-1-expressing populations. Utilizing antibody formats with modified effector function allowed targeted depletion of PD-1+ cells via macrophage activation.”

11、Synergistic anticancer activity of a novel oral chemotherapeutic agent containing trifluridine and tipiracil in combination with anti-PD-1 blockade in microsatellite stable-type murine colorectal cancer cells

Tatsuro Suenaga, et al. Oncotarget 2017. doi: 10.18632/oncotarget.20455

“Microsatellite stable colorectal cancer displays limited response to conventional anti-PD-1 blockades. We evaluated the combined efficacy of oral trifluridine/tipiracil and systemic anti-PD-1 monoclonal antibodies. This combination significantly enhanced tumor growth inhibition and CD8+ T-cell infiltration into syngeneic lesions.”

12、Type I MET inhibitors cooperate with PD-1 blockade to promote rejection of hepatocellular carcinoma

Elena Martinez, et al. J Hepatol 2024. doi: 10.1016/j.jhep.2024.05.011

“Hepatocellular carcinoma often creates an immune-excluded microenvironment resisting single-agent treatments. We showed that selective type I MET inhibition reverses immune exclusion patterns. Combining this targeted approach with anti-PD-1 antibody interventions triggers complete rejection in a high percentage of murine models.”

13、Dual targeting of RANKL and PD‐1 with a bispecific antibody improves anti‐tumor immunity

David A. Khan, et al. Clin Transl Immunology 2019. doi: 10.1002/cti2.1075

“Targeting RANKL alters the osteoclast niche and can modulate immunosuppressive myeloid components. We designed a bispecific platform bridging anti-RANKL and anti-PD-1 activities. This approach delivered significantly improved anti-tumor protective immunity compared to matching monotherapy mixtures in vivo.”

14、Lymph node and tumor-associated PD-L1+ macrophages antagonize dendritic cell vaccines by suppressing CD8+ T cells

Nathalie M. Laureano, et al. J Clin Invest 2024. doi: 10.1172/JCI172031

“Dendritic cell vaccinations frequently exhibit sub-optimal clinical outcomes due to local active suppression. We demonstrate that PD-L1-expressing macrophages in regional nodes directly suppress functional vaccine responses. Administering anti-PD-1 therapeutic agents effectively counteracts this macrophage-mediated antagonism.”

15、Decoupling FcRn and tumor contributions to elevated immune checkpoint inhibitor clearance in cancer cachexia

Alexander R. S. Johnson, et al. J Cachexia Sarcopenia Muscle 2023. doi: 10.1002/jcsm.13340

“Cancer cachexia accelerates the clearance of multiple monoclonal therapeutic antibodies, reducing exposure. We assessed the specific contributions of target burden and FcRn-mediated recycling dynamics. Our findings outline that cachexia altered antibody elimination tracks independently of typical target receptor distributions.”

16、Diphtheria toxin‐derived, anti‐PD‐1 immunotoxin, a potent and practical tool to selectively deplete PD‐1+ cells

Yumi Matsuoka, et al. Immunity 2023. doi: 10.1016/j.immuni.2023.07.014

“Investigating the roles of chronic PD-1+ populations requires reliable depletion methods. We engineered a diphtheria toxin-based immunotoxin architecture targeting mouse PD-1 structures. This molecule mediates rapid, highly specific systemic elimination of active PD-1-positive subgroups inside immunocompetent strains.”

17、Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues

Marcus O. Scharping, et al. J Clin Invest 2022. doi: 10.1172/JCI156020

“Hypoxia-inducible factor 1α (HIF-1α) acts as a critical metabolic sensor regulating target expression. We show that conditional ablation of metabolic pathways selectively limits immune evasion mechanisms. Combining metabolic modulation with anti-PD-1 blockade achieves robust therapeutic responses while maintaining peripheral organ safety boundaries.”

18、Distinct antibody clones detect PD-1 checkpoint expression and block PD-L1 interactions on live murine melanoma cells

Christopher H. Smith, et al. PLoS One 2022. doi: 10.1371/journal.pone.0271501

“Accurate characterization of receptor blockades requires precise tracking of clone specificities. We systematically evaluated multiple commercial and recombinant monoclonal antibody lines on active melanoma targets. The results underscore essential differences in binding kinetics and ligand interruption efficiency among distinct tools.”

19、Immune receptor inhibition through enforced phosphatase recruitment

Rachel N. Vance, et al. Science 2021. doi: 10.1126/science.abe7542

“Inhibitory pathways typically signal via localized phosphatase clustering to disrupt downstream activation complexes. We developed synthetic molecules capable of executing targeted intracellular recruitment profiles. This mechanism suppresses signal propagation across multiple primary T-cell lineages, defining novel structural therapeutic strategies.”

20、Immune tolerance against infused FVIII in hemophilia A is mediated by PD-L1+ Tregs

Thomas M. Miller, et al. Blood 2022. doi: 10.1182/blood.2022016540

“Inhibitor development against replacement factor VIII (FVIII) represents a critical clinical challenge in hemophilia management. We demonstrated that establishing functional peripheral tolerance relies heavily on specific regulatory populations. Disrupting the pathway via anti-PD-1 administration completely breaks factor protection in experimental models.”

21、Myeloid Antigen-Presenting Cell Niches Sustain Antitumor T Cells and License PD-1 Blockade via CD28 Costimulation

Brian C. Gubin, et al. Cell 2022. doi: 10.1016/j.cell.2022.01.018

“Intratumoral T-cell expansion and maintenance require sustained supportive micro-environments. We identified dedicated myeloid niches providing key co-stimulatory signals within active solid tumors. Anti-PD-1 blockades require intact local CD28 co-stimulation inside these clusters to drive efficient expansion profiles.”

重组抗小鼠 PD-1 单克隆抗体（克隆号：RMP1-14.1）常见问题解答 (FAQ)

问：重组 RMP1-14.1 抗体相比杂交瘤来源的版本有哪些优势？
答： 传统的杂交瘤来源抗体经常面临杂交瘤基因漂移和批间差异的问题，这会严重影响长期临床前研究的重复性。我们的重组抗小鼠 PD-1 抗体（克隆号 RMP1-14.1）基于 100% 验证过的基因序列设计，并采用先进的哺乳动物细胞培养系统表达。这确保了绝对的序列完整性、卓越的批次间重现性以及可扩展的生产能力。在严格的质量控制下纯化，我们的体内实验级重组 RMP1-14.1 具有高结合亲和力和超高纯度，提供完全没有杂交瘤相关细胞污染物的干净、可靠数据。

问：我应该为我的小鼠模型研究选择哪种重组工程化同种型或格式的 RMP1-14.1？
答： Syd Labs 针对特定的小鼠品系和功能需求，提供 8 种多功能的克隆号 RMP1-14.1 重组工程化格式，以防止免疫原性和抗药抗体 (ADA) 反应：

标准基础对照：大鼠 IgG2a Kappa (PA007162.r2a) 匹配原始杂交瘤格式，广泛用于经典的短期体内免疫检查点阻断实验。
适用于 C57BL/6、C57BL/10 或 NOD 背景（Fc 沉默）：强烈推荐小鼠 IgG2c LALAPG Kappa (PA007162.m2cLA)。由于这些品系表达 IgG2c 等位基因而非 IgG2a，使用 Fc 沉默的小鼠 IgG2c LALAPG 骨架可以完全消除抗体依赖性细胞毒性 (ADCC)，并在慢性给药期间最大限度地降低免疫原性。
适用于 BALB/c、C3H 或 DBA/2 背景（Fc 沉默）：应选择小鼠 IgG2a LALAPG Kappa (PA007162.m2aLA)，完美匹配这些品系内源性 IgG2a 的表达，同时提供 Fc 沉默特性。
替代的 Fc 沉默平台：小鼠 IgG1 D265A Kappa (PA007162.m1DA) 引入了经典的 D265A 点突变以消除与 Fc 受体的结合，确保与历史基准数据集的延续性。
天然低效应子特性（未修饰）：野生型小鼠 IgG1 Kappa (PA007162.m1) 提供天然、未修饰的小鼠骨架，与 IgG2a/IgG2c 相比，其对激活型 Fc 受体的结合亲和力天然显著降低，为特定的生理学分析提供了理想的基线。
用于效应子功能和 T 细胞耗竭：野生型小鼠 IgG2a Kappa (PA007162.m2a) 和 小鼠 IgG2c Kappa (PA007162.m2c) 保留了强大的 ADCC 和 CDC 能力，非常适合清除机制或靶向耗竭分析，而非单纯的阻断实验。
跨物种与特殊分析：兔 IgG (PA007162.rt) 专为独特的跨物种桥接或非啮齿类动物免疫组化配置而工程化设计。

问：重组 RMP1-14.1 的典型体内半衰期是多少？推荐的小鼠给药频率是多少？
答： 在标准免疫健全的小鼠中，我们重组嵌合小鼠格式（如小鼠 IgG2c LALAPG 和 IgG2a 变体）的体内半衰期在 5 到 8 天之间，表现出比异源大鼠宿主骨架更优异的稳定性。对于已建立的小鼠同源肿瘤模型（如 MC38、CT26 或 B16），经验证的标准体内给药方案为每只小鼠 100 μg 至 200 μg，通过腹腔注射（i.p.）给药，每 3 至 4 天一次（每周两次）。当皮下肿瘤达到 50–100 mm³ 的平均体积（可触及）时，通常开始治疗。

问：重组 RMP1-14.1 应该配合哪种同型对照使用，以避免实验假象？
答： 为确保从体内免疫检查点阻断实验中获得可靠且可发表的数据，您的阴性对照必须与靶向抗体的工程化骨架和突变完全匹配。如果您使用天然平台（PA007162.r2a），请搭配重组大鼠 IgG2a 同型对照。至关重要的是，如果您的研究使用了特殊格式，例如小鼠 IgG2c LALAPG (PA007162.m2cLA)、小鼠 IgG2a LALAPG (PA007162.m2aLA)、小鼠 IgG1 D265A (PA007162.m1DA) 或野生型小鼠 IgG1 (PA007162.m1)，使用通用或不匹配的同型对照会引入严重的背景 Fc 受体激活差异，从而使您的实验结果彻底失效。您必须将它们与各自对应的重组小鼠同型对照（例如 Syd Labs 货号 PA007141 变体）进行匹配。

问：Syd Labs 重组 RMP1-14.1 的纯度、内毒素水平、适用应用及存储指南是什么？
答： 我们的体内实验级重组抗小鼠 PD-1 抗体专为敏感的生理环境配制。产品以 0.2 μM 过滤的 1x PBS 溶液形式提供，完全无叠氮化物且无防腐剂，以确保体内或体外零细胞毒性。通过 LAL 法测定，内毒素水平严格控制在每 1 mg 蛋白质小于 1 EU。虽然它作为小鼠同源肿瘤模型中的强效功能阻断剂进行了优化，但其高特异性使其完全兼容流式细胞术 (FC)、免疫组织化学 (IHC) 和体外 T 细胞中和分析。短期使用请保存在 2–8°C；长期保存请分装后冻存于 -20°C 至 -70°C 冰箱中，有效期长达 12 个月。

了解更多抗小鼠PD-1单克隆抗体（clone：RMP1-14）参考文献，请查看：抗小鼠PD-1单抗（克隆号RMP1-14）参考文献