CB17-SCID-Ces1c-KO Mouse
Product Name
CB17-SCID-Ces1c-KO Mouse
Product ID
C001972
Strain Name
CB17-SCID-Ces1cem1/Cya
Backgroud
C.B-17
Status
When using this mouse strain in a publication, please cite “CB17-SCID-Ces1c-KO Mouse (Catalog C001972) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
Ee1, Es1, Es4, EsN, Ee-1, Es-4, Es-N, PESN, Ces-N
NCBI ID
Chromosome
Chr 8
MGI ID
Datasheet
Strain Description
Ces1c, the mouse carboxylesterase 1C (Carboxylesterase 1C) gene, encodes an enzyme highly expressed in rodent plasma, responsible for hydrolyzing various ester- or amide-containing drugs, particularly cleavable linkers (Linker) in antibody-drug conjugates (ADCs) such as Val-Cit (VC) linkers [1-2]. Mouse Ces1c causes non-specific hydrolysis of ADCs in plasma, accelerating drug clearance and severely deviating pharmacokinetic (PK) profiles from human reality [3-4]. In humans, CES1 and CES2 are mainly distributed in the liver and intestine, with negligible activity in plasma, whereas mouse Ces1c, lacking an endoplasmic reticulum retention signal, is secreted in large amounts into plasma [3-4]. Besides its role in drug metabolism, Ces1c is also involved in physiological processes such as lipid metabolism. Studies show that, in evaluating VC-based ADCs, Ces1c in mouse plasma miscleaves the VC-PABC structure, causing premature release of toxic payloads, resulting in systemic toxicity and underestimation of antitumor activity [5-9].
In preclinical evaluation of ADCs, differences in immunodeficient strain backgrounds affect the biodistribution, clearance rates, and reliability of PK/PD results for humanized antibodies [10-15]. For example, highly immunodeficient NOD-SCID and its derivative strains, due to enhanced Fc-FcγR interactions, lead to shortened serum half-life of ADCs and increased off-target organ trapping, thereby underestimating antitumor activity [10-15]. In contrast, the CB17-SCID background exhibits superior characteristics in maintaining antibody half-life and optimizing biodistribution, providing more reliable efficacy data [13-15].
The CB17-SCID-Ces1c-KO mouse is a gene knockout (KO) model, generated on the CB17-SCID immunodeficient background with excellent PK/PD properties, using gene editing technology to knock out the Ces1c gene in mice. This model can be used for ADC drug development, particularly for evaluating VC linker drugs, and to avoid non-specific interference in mouse plasma, providing more clinically predictive efficacy data.
Reference
Lian J, Nelson R, Lehner R. Carboxylesterases in lipid metabolism: from mouse to human. Protein Cell. 2018 Feb;9(2):178-195. doi: 10.1007/s13238-017-0437-z. Epub 2017 Jul 4. PMID: 28677105; PMCID: PMC5818367.
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.
Holmes RS, Wright MW, Laulederkind SJ, Cox LA, Hosokawa M, Imai T, Ishibashi S, Lehner R, Miyazaki M, Perkins EJ, Potter PM, Redinbo MR, Robert J, Satoh T, Yamashita T, Yan B, Yokoi T, Zechner R, Maltais LJ. Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins. Mamm Genome. 2010 Oct;21(9-10):427-41. doi: 10.1007/s00335-010-9284-4. Epub 2010 Oct 8. PMID: 20931200; PMCID: PMC3127206.
Di L. The Impact of Carboxylesterases in Drug Metabolism and Pharmacokinetics. Curr Drug Metab. 2019;20(2):91-102. doi: 10.2174/1389200219666180821094502. PMID: 30129408; PMCID: PMC6635651.
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.
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.
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.
Strain Strategy
The 5th exon region of the Ces1c gene in mice was knocked out using gene editing technology.
Figure 1. Schematic diagram of the gene-editing strategy for CB17-SCID-Ces1c-KO mice.
Application Area
Preclinical pharmacokinetic (PK), linker stability, payload release efficiency, and in vivo antitumor activity evaluation of ADC drugs;
Avoiding species-specific metabolic interference in traditional immunodeficient mice when evaluating cleavable linkers like VC, providing more accurate data for clinical translation predictions.
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