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CB17-SCID-Ces1c-KO小鼠

复苏/繁育服务

产品名称

CB17-SCID-Ces1c-KO

产品编号

C001972

品系全称

CB17-SCID-Ces1c^em1/Cya

品系背景

C.B-17

品系状态

使用本品系发表的文献需注明： CB17-SCID-Ces1c-KO mice (Catalog C001972) were purchased from Cyagen.

交付类型

周龄

性别

基因型

数量

小计：

询价

其他免疫缺陷模型

基本信息

应用领域

验证数据

基因

Ces1c

基因别称

NCBI ID

13884

染色体号

Chr 8

MGI ID

MGI:95420

更多详情

RDDC综合数据库 >>

品系介绍

小鼠羧酸酯酶1C (Carboxylesterase 1C, Ces1c) 基因编码一种在啮齿类动物血浆中高表达的酶，负责水解多种含酯键或酰胺键的药物，特别是抗体偶联药物 (ADC) 中的可裂解连接子 (Linker) 如Val-Cit (VC) 连接子 ^[1-2]。小鼠Ces1c会导致ADC在血浆中发生非特异性水解，加速药物清除，并导致药代动力学 (PK) 特征严重偏离人类真实情况 ^[3-4]。在人类中，CES1和CES2主要分布在肝脏和肠道，血浆中活性几乎忽略不计，而小鼠Ces1c因缺乏内质网滞留信号，大量分泌至血浆中 ^[3-4]。Ces1c除了在药物代谢中的作用，还参与脂质代谢等生理过程。研究表明，在评估基于VC连接子的ADC时，小鼠血浆中的Ces1c会误切VC-PABC结构，导致毒性载荷提前释放，造成系统性毒性并低估抗肿瘤活性 ^[5-9]。

在ADC临床前评估中，不同免疫缺陷品系的背景差异会影响人源化抗体的生物分布、清除速率及PK/PD结果的可靠性 ^[10-15]。例如，高度免疫缺陷的NOD-SCID及其衍生品系因Fc-FcγR交互增强，导致ADC的血清半衰期缩短和非靶器官截留增加，从而低估抗肿瘤活性 ^[10-15]。相比之下，CB17-SCID背景在维持抗体半衰期和优化生物分布方面表现出更优特性，提供更可靠的药效数据 ^[13-15]。

CB17-SCID-Ces1c-KO小鼠是Ces1c基因敲除 (KO) 模型，在CB17-SCID这一具备优异PK/PD特性的免疫缺陷背景上，利用基因编辑技术敲除了小鼠体内Ces1c基因。该模型可用于ADC药物研发，特别是VC类Linker药物评价，以及规避小鼠血浆非特异性干扰，提供更具临床预测性的药效数据。

参考文献

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Nagaoka M, Sakai Y, Nakajima M, Fukami T. Role of carboxylesterase and arylacetamide deacetylase in drug metabolism, physiology, and pathology. Biochem Pharmacol. 2024 May;223:116128. doi: 10.1016/j.bcp.2024.116128. Epub 2024 Mar 15. PMID: 38492781.

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NJ Bio, Inc. (2025, December 31). Recent advances in ADCs. NJ Bio. https://njbio.com/antibody-drug-conjugates/

Crescioli S, Kaplon H, Chenoweth A, Hsu YS, Pinto K, Kapoor V, Reichert JM. Antibodies to watch in 2026. MAbs. 2026 Dec;18(1):2614669. doi: 10.1080/19420862.2026.2614669. Epub 2026 Jan 21. PMID: 41560619; PMCID: PMC12826703.

Gao Y, Xia Y, Chen Y, Zhou S, Fang Y, Yu J, Zhang L, Sun L. Key considerations based on pharmacokinetic/pharmacodynamic in the design of antibody-drug conjugates. Front Oncol. 2025 Jan 9;14:1459368. doi: 10.3389/fonc.2024.1459368. PMID: 39850824; PMCID: PMC11754052.

Anami Y, Yamazaki CM, Xiong W, Gui X, Zhang N, An Z, Tsuchikama K. Glutamic acid-valine-citrulline linkers ensure stability and efficacy of antibody-drug conjugates in mice. Nat Commun. 2018 Jun 28;9(1):2512. doi: 10.1038/s41467-018-04982-3. PMID: 29955061; PMCID: PMC6023893.

Dorywalska M, Dushin R, Moine L, Farias SE, Zhou D, Navaratnam T, Lui V, Hasa-Moreno A, Casas MG, Tran TT, Delaria K, Liu SH, Foletti D, O'Donnell CJ, Pons J, Shelton DL, Rajpal A, Strop P. Molecular Basis of Valine-Citrulline-PABC Linker Instability in Site-Specific ADCs and Its Mitigation by Linker Design. Mol Cancer Ther. 2016 May;15(5):958-70. doi: 10.1158/1535-7163.MCT-15-1004. Epub 2016 Mar 4. PMID: 26944918.

Li F, Ulrich ML, Shih VF, Cochran JH, Hunter JH, Westendorf L, Neale J, Benjamin DR. Mouse Strains Influence Clearance and Efficacy of Antibody and Antibody-Drug Conjugate Via Fc-FcγR Interaction. Mol Cancer Ther. 2019 Apr;18(4):780-787.

Sharma SK, Chow A, Monette S, Vivier D, Pourat J, Edwards KJ, Dilling TR, Abdel-Atti D, Zeglis BM, Poirier JT, Lewis JS. Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models. Cancer Res. 2018 Apr 1;78(7):1820-1832.

Oldham RJ, Mockridge CI, James S, Duriez PJ, Chan HTC, Cox KL, Pitic VA, Glennie MJ, Cragg MS. FcγRII (CD32) modulates antibody clearance in NOD SCID mice leading to impaired antibody-mediated tumor cell deletion. J Immunother Cancer. 2020 Jun;8(1):e000619.

Laurentiu Pop, Xiao-yun Liu, Iliodora Pop, Ellen Vitetta; Abnormally short serum half-lives of chimeric and human IgGs in NOD-SCID mice (P4184). J Immunol 1 May 2013; 190 (1_Supplement): 48.2. https://doi.org/10.4049/jimmunol.190.Supp.48.2.

Fu Li, Michelle Ulrich, Joshua Hunter, Lori Westendorf, Devra Olson, Cassie Baker Lee, Dennis Benjamin, Che-Leung Law. Fc-FcγR interaction impacts the clearance and antitumor activity of antibody-drug conjugates in NSG mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2082.