2,896
Views
18
CrossRef citations to date
0
Altmetric
Report

Preclinical and translational pharmacokinetics of a novel THIOMAB™ antibody-antibiotic conjugate against Staphylococcus aureus

, , , ORCID Icon, , , ORCID Icon, , , & show all
Pages 1162-1174 | Received 21 Feb 2019, Accepted 30 May 2019, Published online: 20 Jun 2019

References

  • DeLeo FR, Chambers HF. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest. 2009;119:2464–674. doi:10.1172/JCI38226.
  • van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012;25:362–86. doi:10.1128/CMR.05022-11.
  • Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28:603–61. doi:10.1128/CMR.00134-14.
  • Thwaites GE, Gant V. Are bloodstream leukocytes Trojan Horses for the metastasis of Staphylococcus aureus?. Nat Rev Microbiol. 2011;9:215–22. doi:10.1038/nrmicro2508.
  • Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, DePalatis L, Raab H, Hazenbos WL, Morisaki JH, et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature. 2015;527:323–28. doi:10.1038/nature16057.
  • Mariathasan S, Tan MW. Antibody-antibiotic conjugates: A novel therapeutic platform against bacterial infections. Trends Mol Med. 2017;23:135–49. doi:10.1016/j.molmed.2016.12.008.
  • Shen BQ, Xu K, Liu L, Raab H, Bhakta S, Kenrick M, Parsons-Reponte KL, Tien J, Yu S-F, Mai E, et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat Biotechnol. 2012;30:184–89. doi:10.1038/nbt.2108.
  • Zhou C, Lehar S, Gutierrez J, Rosenberger CM, Ljumanovic N, Dinoso J, Koppada N, Hong K, Baruch A, Carrasco-Triguero M, et al. Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMAB antibody antibiotic conjugate against Staphylococcus aureus in mice. mAbs. 2016;8:1612–19. doi:10.1080/19420862.2016.1229722.
  • Kaur S, Xu K, Saad OM, Dere RC, Carrasco-Triguero M. Bioanalytical assay strategies for the development of antibody-drug conjugate biotherapeutics. Bioanalysis. 2013;5:201–26. doi:10.4155/bio.12.299.
  • Sukumaran S, Zhang C, Leipold DD, Saad OM, Xu K, Gadkar K, Samineni D, Wang B, Milojic-Blair M, Carrasco-Triguero M, et al. Development and translational application of an integrated, mechanistic model of antibody-drug conjugate pharmacokinetics. Aaps J. 2017;19:130–40. doi:10.1208/s12248-016-9993-z.
  • Deng R, Iyer S, Theil FP, Mortensen DL, Fielder PJ, Prabhu S. Projecting human pharmacokinetics of therapeutic antibodies from nonclinical data: what have we learned? mAbs. 2011;3:61–66. doi:10.4161/mabs.3.1.13799.
  • Hotzel I, Theil FP, Bernstein LJ, Prabhu S, Deng R, Quintana L, Lutman J, Sibia R, Chan P, Bumbaca D, et al. A strategy for risk mitigation of antibodies with fast clearance. mAbs. 2012;4:753–60. doi:10.4161/mabs.22189.
  • Sukumaran S, Gadkar K, Zhang C, Bhakta S, Liu L, Xu K, Raab H, Yu S-F, Mai E, Fourie-O’Donohue A, et al. Mechanism-based pharmacokinetic/pharmacodynamic model for THIOMAB drug conjugates. Pharm Res. 2015;32:1884–93. doi:10.1007/s11095-014-1582-1.
  • Peck M, Rothenberg ME, Deng R, Lewin-Koh N, She G, Kamath AV, Carrasco-Triguero M, Saad O,Castro A,Teufel L, et al. A Phase 1, Randomized, Single-Ascending-Dose Study To Investigate the Safety, Tolerability, and Pharmacokinetics of DSTA4637S, an Anti-Staphylococcus aureus Thiomab Antibody-Antibiotic Conjugate, in Healthy Volunteers. Antimicrob Agents Chemother. 2019 May 24;63(6). pii: e02588-18. doi:10.1128/AAC.02588-18
  • Deng R, Jin F, Prabhu S, Iyer S. Monoclonal antibodies: what are the pharmacokinetic and pharmacodynamic considerations for drug development? Expert Opin Drug Metab Toxicol. 2012;8:141–60. doi:10.1517/17425255.2012.643868.
  • Ryman JT, Meibohm B. Pharmacokinetics of monoclonal antibodies. Cpt. 2017;6:576–88.
  • Kamath AV, Iyer S. Challenges and advances in the assessment of the disposition of antibody-drug conjugates. Biopharm Drug Dispos. 2016;37:66–74. doi:10.1002/bdd.1957.
  • Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG, Kissler KM, Bernhardt SX, Kopcha AK, Zabinski RF, et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res. 2004;10:7063–70. doi:10.1158/1078-0432.CCR-04-0789.
  • Kamath AV, Iyer S. Preclinical pharmacokinetic considerations for the development of antibody drug conjugates. Pharm Res. 2015;32:3470–79. doi:10.1007/s11095-014-1584-z.
  • Lu D, Girish S, Gao Y, Wang B, Yi JH, Guardino E, Samant M, Cobleigh M, Rimawi M, Conte P, et al. Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer: clinical implications of the effect of covariates. Cancer Chemother Pharmacol. 2014;74:399–410. doi:10.1007/s00280-014-2500-2.
  • Suri A, Mould DR, Liu Y, Jang G, Venkatakrishnan K. Population PK and exposure-response relationships for the antibody-drug conjugate brentuximab vedotin in CTCL patients in the phase III ALCANZA study. Clin Pharmacol Ther. 2018;104:989–99. doi:10.1002/cpt.1037.
  • Bender B, Leipold DD, Xu K, Shen BQ, Tibbitts J, Friberg LE. A mechanistic pharmacokinetic model elucidating the disposition of trastuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC) for treatment of metastatic breast cancer. Aaps J. 2014;16:994–1008. doi:10.1208/s12248-014-9618-3.
  • Lu D, Jin JY, Girish S, Agarwal P, Li D, Prabhu S, Dere RC, Saad OM, Nazzal D, Koppada N, et al. Semi-mechanistic multiple-analyte pharmacokinetic model for an antibody-drug-conjugate in cynomolgus monkeys. Pharm Res. 2015;32:1907–19. doi:10.1007/s11095-014-1585-y.
  • Shah DK, Haddish-Berhane N, Betts A. Bench to bedside translation of antibody drug conjugates using a multiscale mechanistic PK/PD model: a case study with brentuximab-vedotin. J Pharmacokinet Pharmacodyn. 2012;39:643–59. doi:10.1007/s10928-012-9276-y.
  • Khot A, Tibbitts J, Rock D, Shah DK. Development of a translational physiologically based pharmacokinetic model for antibody-drug conjugates: A case study with T-DM1. Aaps J. 2017;19:1715–34. doi:10.1208/s12248-017-0131-3.
  • Lu D, Gibiansky L, Agarwal P, Dere RC, Li C, Chu YW, et al. Integrated two-analyte population pharmacokinetic model for antibody-drug conjugates in patients: implications for reducing pharmacokinetic sampling. CPT Pharmacometrics Syst Pharmacol. 2016;5:665–73.
  • Xu K, Liu L, Saad OM, Baudys J, Williams L, Leipold D, Shen B, Raab H, Junutula JR, Kim A, et al. Characterization of intact antibody-drug conjugates from plasma/serum in vivo by affinity capture capillary liquid chromatography-mass spectrometry. Anal Biochem. 2011;412:56–66. doi:10.1016/j.ab.2011.01.004.
  • Sun X, Ponte JF, Yoder NC, Laleau R, Coccia J, Lanieri L, Qiu Q, Wu R, Hong E, Bogalhas M, et al. Effects of drug-antibody ratio on pharmacokinetics, biodistribution, efficacy, and tolerability of antibody-maytansinoid conjugates. Bioconjug Chem. 2017;28:1371–81. doi:10.1021/acs.bioconjchem.7b00062.
  • Dong JQ, Salinger DH, Endres CJ, Gibbs JP, Hsu CP, Stouch BJ, Hurh E, Gibbs MA. Quantitative prediction of human pharmacokinetics for monoclonal antibodies: retrospective analysis of monkey as a single species for first-in-human prediction. Clin Pharmacokinet. 2011;50:131–42. doi:10.2165/11537430-000000000-00000.
  • Ling J, Zhou H, Jiao Q, Davis HM. Interspecies scaling of therapeutic monoclonal antibodies: initial look. J Clin Pharmacol. 2009;49:1382–402. doi:10.1177/0091270009337134.
  • Wang J, Iyer S, Fielder PJ, Davis JD, Deng R. Projecting human pharmacokinetics of monoclonal antibodies from nonclinical data: comparative evaluation of prediction approaches in early drug development. Biopharm Drug Dispos. 2016;37:51–65. doi:10.1002/bdd.1952.
  • Wang W, Prueksaritanont T. Prediction of human clearance of therapeutic proteins: simple allometric scaling method revisited. Biopharm Drug Dispos. 2010;31:253–63.
  • Li C, Zhang C, Deng R, Leipold D, Li D, Latifi B, Gao Y, Zhang C, Li Z,Miles D, et al. Prediction of human pharmacokinetics of antibody-drug conjugates from nonclinical data. Clin Transl Sci. 2019 May 22. doi:10.1111/cts.12649.
  • Haddish-Berhane N, Shah DK, Ma D, Leal M, Gerber HP, Sapra P, Barton HA, Betts AM. On translation of antibody drug conjugates efficacy from mouse experimental tumors to the clinic: a PK/PD approach. J Pharmacokinet Pharmacodyn. 2013;40:557–71. doi:10.1007/s10928-013-9329-x.
  • Bouillon-Pichault M, Brillac C, Amara C, Nicolazzi C, Fagniez N, Fau JB, Koiwai K, Ziti-Ljajic S, Veyrat-Follet C. Translational model-based strategy to guide the choice of clinical doses for antibody-drug conjugates. J Clin Pharmacol. 2017;57:865–75. doi:10.1002/jcph.869.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.