模型	内源性启动子	最长的半衰期	评价 PK 值的细微差异	免疫缺陷	白蛋白 PK
FcRn Tg32 (014565)	是	是	否	否	否
FcRn Tg276 (004919)	否	否	是	否	否
Tg32 Scid (018441)	是	是	否	是	否
Tg276 Scid* (021146)	否	否	是	是	否
Tg276 Rag1* (016919)	否	否	是	是	否
Tg32 Alb KO (025201)	是	是	否	否	是

*需冷冻复苏

 

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Avery LB, Wang M, Kavosi MS, Joyce A, Kurz JC, Fan YY, Dowty ME, Zhang M, Zhang Y, Cheng A, Hua F, Jones HM, Neubert H, Polzer RJ, O'Hara DM. 2016. Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. MAbs. 8(6):1064-78. PMID: 27232760

 

Fan YY, Avery LB, Wang M, O'Hara DM, Leung S, Neubert H. 2016. Tissue expression profile of human neonatal Fc receptor (FcRn) in Tg32 transgenic mice. MAbs. 8(5):848-53. PMID: 27104806

 

Hamblett KJ, Le T, Rock BM, Rock DA, Siu S, Huard JN, Conner KP, Milburn RR, O'Neill JW, Tometsko ME, Fanslow WC. 2016. Altering Antibody-Drug Conjugate Binding to the Neonatal Fc Receptor Impacts Efficacy and Tolerability. Mol Pharm. 13(7):2387-96. PMID: 27248573

 

Haraya K, Tachibana T, Iwayanagi Y, Maeda A, Ozeki K, Nezu J, Ishigai M, Igawa T. 2016. PK/PD analysis of a novel pH-dependent antigen-binding antibody using a dynamic antibody-antigen binding model. Drug Metab Pharmacokinet. 31(2):123-32. PMID: 26944099

 

Low BE, Wiles MV. 2016. A Humanized Mouse Model to Study Human Albumin and Albumin Conjugates Pharmacokinetics. Methods Mol Biol. 1438:115-22. PMID: 27150087

 

Roopenian DC, Christianson GJ, Proetzel G, Sproule TJ. 2016. Human FcRn Transgenic Mice for Pharmacokinetic Evaluation of Therapeutic Antibodies. Methods Mol Biol. 1438:103-14. PMID: 27150086

 

Abdiche YN; Yeung YA; Chaparro-Riggers J; Barman I; Strop P; Chin SM; Pham A; Bolton G; McDonough D; Lindquist K; Pons J; Rajpal A. 2015. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity. MAbs. 7(2):331-43. PMID: 25658443

 

Roopenian DC; Low BE; Christianson GJ; Proetzel G; Sproule TJ; Wiles MV. 2015. Albumin-deficient mouse models for studying metabolism of human albumin and pharmacokinetics of albumin-based drugs. MAbs. 7(2):344-51. PMID: 25654695

 

Haraya K; Tachibana T; Nanami M; Ishigai M. 2014. Application of human FcRn transgenic mice as a pharmacokinetic screening tool of monoclonal antibody. Xenobiotica. 44(12):1127-34. PMID: 25030041

 

Powner MB; McKenzie JA; Christianson GJ; Roopenian DC; Fruttiger M. 2014. Expression of neonatal Fc receptor in the eye. Invest Ophthalmol Vis Sci. 55(3):1607-15. PMID: 24550358

 

Monnet C; Jorieux S; Souyris N; Zaki O; Jacquet A; Fournier N; Crozet F; de Romeuf C; Bouayadi K; Urbain R; Behrens CK; Mondon P; Fontayne A. 2014. Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody. MAbs. 6(2):422-36. PMID: 24492301

 

Proetzel G; Wiles MV; Roopenian DC. 2014. Genetically engineered humanized mouse models for preclinical antibody studies. BioDrugs. 28(2):171-80. PMID: 24150980

 

Proetzel G; Roopenian DC. 2014. Humanized FcRn mouse models for evaluating pharmacokinetics of human IgG antibodies. Methods. 65(1):148-53. PMID: 23867339

 

Igawa T, Maeda A, Haraya K, Tachibana T, Iwayanagi Y, Mimoto F, Higuchi Y, Ishii S, Tamba S, Hironiwa N, Nagano K, Wakabayashi T, Tsunoda H, Hattori K. 2013. Engineered monoclonal antibody with novel antigen-sweeping activity in vivo. PLoS One. 8(5):e63236. PMID: 23667591

 

Tam SH; McCarthy SG; Brosnan K; Goldberg KM; Scallon BJ. 2013. Correlations between pharmacokinetics of IgG antibodies in primates vs. FcRn-transgenic mice reveal a rodent model with predictive capabilities. MAbs. 5(3):397-405. PMID: 23549129

 

Gehlsen K; Gong R; Bramhill D; Wiersma D; Kirkpatrick S; Wang Y; Feng Y; Dimitrov DS. 2012. Pharmacokinetics of engineered human monomeric and dimeric CH2 domains. MAbs. 4(4):466-74. PMID: 22699277

 

Andersen JT; Foss S; Kenanova VE; Olafsen T; Leikfoss IS; Roopenian DC; Wu AM; Sandlie I. 2012. Anti-carcinoembryonic antigen single-chain variable fragment antibody variants bind mouse and human neonatal Fc receptor with different affinities that reveal distinct cross-species differences in serum half-life. J Biol Chem. 287(27):22927-37. PMID: 22570488

 

Christianson GJ; Sun VZ; Akilesh S; Pesavento E; Proetzel G; Roopenian DC. 2012. Monoclonal antibodies directed against human FcRn and their applications. MAbs. 4(2):208-16. PMID: 22453095

 

Stein C; Kling L; Proetzel G; Roopenian DC; de Angelis MH; Wolf E; Rathkolb B. 2012. Clinical chemistry of human FcRn transgenic mice. Mamm Genome. 23(3-4):259-69. PMID: 22193411

 

Liu L; Stadheim A; Hamuro L; Pittman T; Wang W; Zha D; Hochman J; Prueksaritanont T. 2011. Pharmacokinetics of IgG1 monoclonal antibodies produced in humanized Pichia pastoris with specific glycoforms: a comparative study with CHO produced materials. Biologicals. 39(4):205-10. PMID: 21723741

 

Wang W; Vlasak J; Li Y; Pristatsky P; Fang Y; Pittman T; Roman J; Wang Y; Prueksaritanont T; Ionescu R. 2011. Impact of methionine oxidation in human IgG1 Fc on serum half-life of monoclonal antibodies. Mol Immunol. 48(6-7):860-6. PMID: 21256596

 

Roopenian DC; Christianson GJ; Sproule TJ. 2010. Human FcRn transgenic mice for pharmacokinetic evaluation of therapeutic antibodies. Methods Mol Biol 602:93-104. PMID: 20012394 

 

Zalevsky J; Chamberlain AK; Horton HM; Karki S; Leung IW; Sproule TJ; Lazar GA; Roopenian DC; Desjarlais JR. 2010. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157-9. PMID: 20081867

 

Petkova SB; Akilesh S; Sproule TJ; Christianson GJ; Al Khabbaz H; Brown AC; Presta LG; Meng YG; Roopenian DC. 2006. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 18(12):1759-69. PMID: 17077181 

 

Chaudhury C; Mehnaz S; Robinson JM; Hayton WL; Pearl DK; Roopenian DC; Anderson CL. 2003. The major histocompatibility complexrelated Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 197(3):315-22. PMID: 12566415 

 

Liu XY; Pop LM; Roopenian DC; Ghetie V; Vitetta ES; Smallshaw JE. 2006. Generation and characterization of a novel tetravalent anti-CD22 antibody with improved antitumor activity and pharmacokinetics. Int Immunopharmacol. 6(5):791-9. PMID: 16546710

 

Ober RJ; Radu CG; Ghetie V; Ward ES. 2001. Differences in promiscuity for antibody-FcRn interactions across species: Implications for therapeutic antibodies. Int. Immunol 13(12):1551-9. PubMed: 117171962015 May;16(3):165-72. PMID: 25838158 

 

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• 一项使用了 6 只 B6.Cg-Fcgrt^tm1Dcr Tg(FCGRT)32Dcr/DcrJ (014565) 小鼠的标准研究。
• 实验药物及空白对照均通过 IV（静脉注射）给药。
• 实验药物经 IV 给药后 1、2、6、10、14、18、22 和 26 天采集血样。
• 通过 ELISA 定量分析实验药物的浓度，并使用 PK Solutions 软件计算药代动力学数据。

 

• 一项使用了 6 只 B6.Cg-Fcgrt^tm1Dcr Tg(FCGRT)32Dcr/DcrJ (014565) 小鼠的标准研究。
• 通过 IV 给予小鼠人 IgG，24 小时后采集血样。
• 采血后 1 小时，通过 IV 给予实验药物和空白对照。
• 32、48、56、72、96、120 和 144 小时后采集血样。
• 通过 ELISA 定量分析人 IgG 或白蛋白的浓度，并使用 PK Solutions 软件计算药效学数据。