Antitumor effects of pingyangmycin conjugated with Fab́ fragment of monoclonal antibody

Xiao Yun Liu, Xiu Jun Liu, Yi Li, Wei Gang Wang, Yong Su Zhen

Research output: Contribution to journalArticle

Abstract

AIM To develop an immunoconjugate with targeting antitumor effects by linking the Fab́ fragment of McAb to pingyangmycin (PYM). METHODS McAb 3A5 was digested with pepsin to obtain Fab́ fragment. Linking between Fab́ and PYM was mediated by dextran T-40. Immunoreactivity of Fab́ was determined by ELISA. Bacteria inhibitory activity of the conjugate was determined by TTC assay. Cytotoxicity to carcinoma cells was determined by MTT assay and antitumor effects in vivo were assessed in BALB/c mice transplanted with colon carcinoma 26(C26). RESULTS The Fab́-PYM conjugate retained immunoreactivity with C26 cells, the target cells. The IC50 valvues of Fab́-PYM and PYM to C26 cells were 2.51 μg·mL-1 and 32.46 μg·mL-1, respectively. Fab́-PYM and PYM displayed similar cytotoxicity to KB cells, the non-target cells. By intraperitoneal dose of 5 mg·kg-1×6, Fab́-PYM and PYM suppressed the growth of colon carcinoma 26 by 77% and 56%, respectively. By intravenous dose of 5 mg·kg-1×7, Fab́-PYM, 3A5-PYM and PYM inhibited the growth of colon carcinoma 26 by 89%, 73% and 70%, respectively. Fab́-PYM was found to be more effective against target tumor than 3A5-PYM and PYM (P lt;0.01). With higher tolerable dose of 10 mg·kg-1×7, iv, the inhibition of tumor growth by Fab́-PYM reached 91%. CONCLUSION Fab́-PYM conjugate characterized by smaller size of the molecule displayed higher antitumor effects than 3A5-PYM and free PYM.

Original languageEnglish (US)
Pages (from-to)652-653
Number of pages2
JournalYaoxue Xuebao
Volume35
Issue number9
StatePublished - Sep 2000

Keywords

  • Antitumor activity
  • Fab́ fragment
  • Immunoconjugate
  • Monoclonal antibody
  • Pingyangmycin

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Liu, X. Y., Liu, X. J., Li, Y., Wang, W. G., & Zhen, Y. S. (2000). Antitumor effects of pingyangmycin conjugated with Fab́ fragment of monoclonal antibody. Yaoxue Xuebao, 35(9), 652-653.