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Preparation of anti-HER2 monoclonal antibody-paclitaxel immunoconjugate and its biological evaluation

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Summary

Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was prepared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate (FITC), the specific binding of TAX-Sc7301 to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively. TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-Sc7301 concentration (3–48 nmol/L) and the incubation time (P<0.05). It was concluded that the TAX-Sc7301 immunoconjugate is potentially applicable as a targeted agent against HER2-positive tumor cells.

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References

  1. Jaracz S, Chen J, Kuznetsova LV, et al. Recent advances in tumor-targeting anticancer drug conjugates. Bioorg Med Chem, 2005,13(17):5043–5054

    Article  PubMed  CAS  Google Scholar 

  2. Zhao J, Cao SL, Zheng XL, et al. Folate receptor-mediated antitumor drugs. Yaoxue Xuebao (Chinese), 2009,44(9):109–114

    CAS  Google Scholar 

  3. Milenic DE, Brechbiel MW. Targeting of radio-isotopes for cancer therapy. Cancer Biol Ther, 2004,3(4):361–370

    PubMed  CAS  Google Scholar 

  4. Camilleri BS, Hardy-Bessard AC, Le TA, et al. HER2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the gineco group. Ann Oncol, 2004,15(1):104–122

    Article  Google Scholar 

  5. Cao Y, Marks JD, Marks JW, et al. Construction and characterization of novel, recombinant immunotoxins targeting the Her2/neu oncogene product: in vitro and in vivo studies. Cancer Res, 2009,69(23):8987–8995

    Article  PubMed  CAS  Google Scholar 

  6. Mandler R, Kobayashi H, Hinson ER, et al. Herceptin-geldanamycin immunoconjugates: pharmacokinetics, biodistribution, and enhanced antitumor activity. Cancer Res, 2004,64(4):1460–1467

    Article  PubMed  CAS  Google Scholar 

  7. Chen H, Gao J, Lu Y, et al. Preparation and characterization of PE38KDEL-loaded anti-HER2 nanoparticles for targeted cancer therapy. J Control Release, 2008,28(3):209–216

    Article  CAS  Google Scholar 

  8. Moliterni A, Menard S, Valagussa P, et al. HER2 overexpression and doxorubicin in adjuvant chemotherapy for respectable breast cancer. J Clin Oncol, 2003,21(3):458–462

    Article  PubMed  CAS  Google Scholar 

  9. Junttila TT, Tanner M, Isola J. Targeted cytotoxic drugs emerging for cancer therapy. Duodecim, 2011,127(4):343–349

    PubMed  Google Scholar 

  10. Fu Y, Li S, Zu Y, et al. Medicinal chemistry of paclitaxel and its analogues. Curr Med Chem, 2009,16(30):3966–3985

    Article  PubMed  CAS  Google Scholar 

  11. Schrader C, Keussen C, Bewig B, et al. Symptoms and signs of an acute myocardial ischemia caused by chemotherapy with Paclitaxel (Taxol) in a patient with metastatic ovarian carcinoma. Eur J Med Res, 2005,10(11):498–501

    PubMed  Google Scholar 

  12. Cruz A, Temu T, Hines-Telang G, et al. Paclitaxel-induced neutrophilic adverse reaction and acral erythema. Acta Derm Venereol, 2011,91(1):86–87

    PubMed  CAS  Google Scholar 

  13. Rao SC, Chu JJ, Liu RS, et al. Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes. Bioorg Med Chem, 1998,6(11):2193–2204

    Article  PubMed  CAS  Google Scholar 

  14. Erickson HK, Widdison WC, Mayo MF, et al. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem, 2010,21(1):84–92

    Article  PubMed  CAS  Google Scholar 

  15. Burke PJ, Toki BE, Meyer DW, et al. Novel immunoconjugates comprised of streptonigrin and 17-amino-geldanamycin attached via a dipeptide-p-aminobenzyl-amine linker system. Bioorg Med Chem Lett, 2009,19(1):2650–2653

    Article  PubMed  CAS  Google Scholar 

  16. Safavy A, Bonner JA, Waksal HW, et al. Synthesis and biological evaluation of paclitaxel-C225 conjugate as a model for targeted drug delivery. Bioconjug Chem, 2003,14(2):302–310

    Article  PubMed  CAS  Google Scholar 

  17. Liu D, Rao ZCh, Chen ZhC, et al. Killing effect of anti-HER2 monoclonal antibody-TAX immunoconjugate on the tumor cells in vitro. Chin Hosp Pharm J (Chinese), 2007,27(1):10–13

    Google Scholar 

  18. Gao Y, Wu Q, Liang X, et al. Effect of anti-HER-2 engineered antibody chA21 on MMP-2 and TIMP-2 expression of human ovarian cancer SKOV3 cells. J Si’An Jiaotong Univ (Medical Sci), 2007,28(4):368–371

    CAS  Google Scholar 

  19. Huang SS, Liu R, Qu YX, et al. Fluorescent biological label for recognizing human ovarian tumor cells based on fluorescent nanoparticles. J Fluoresc, 2009,19(6):1095–1101

    Article  PubMed  CAS  Google Scholar 

  20. Sun Y, Yu F, Sun BW, et al. Antibody-drug conjugates as targeted cancer therapeutics. Yaoxue Xuebao (Chinese), 2009,44(9):943–952

    Google Scholar 

  21. Weiner LM. An overview of monoclonal antibody therapy of cancer. Semin Oncol, 1999,26(4 Suppl 12):41–50

    PubMed  CAS  Google Scholar 

  22. Martin CG. Targeted drug conjugates: principles and progress. Adv Drug Deliv Rev, 2001,53(2):172–216

    Google Scholar 

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Correspondence to Dong Liu  (刘 东).

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This project was supported by a grant from the National Natural Science Foundation of China (No. 30300429).

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Liu, D., Xu, Y., Rao, Z. et al. Preparation of anti-HER2 monoclonal antibody-paclitaxel immunoconjugate and its biological evaluation. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 735–740 (2011). https://doi.org/10.1007/s11596-011-0669-8

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  • DOI: https://doi.org/10.1007/s11596-011-0669-8

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