Charge-modified single chain antibody constructs of monoclonal antibody CC49: Generation, characterization, pharmacokinetics, and biodistribution analysis

Gabriela Pavlinkova, Guy Beresford, Barbara J.M. Booth, Surinder K. Batra, David Colcher

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

A novel strategy was developed in which an antibody scFv fragment of the monoclonal antibody (MAb) CC49 was modified by engineering DNA coding sequences to lower its isoelectric point. Negatively charged amino acids were added to the carboxy terminus of the CC49 V(H) region by adding nucleotide sequences in a polymerase chain reaction (PCR) amplification of the coding sequence of CC49 scFv. Two new DNA constructs coding for CC49 scFv with lower isoelectric points of 5.8 and 5.2 were engineered. These novel strategy- generated, charge-modified antibody constructs were compared for their immunological, pharmacokinetic, and biodistribution properties in athymic mice bearing LS-174T human colon carcinoma xenografts.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalNuclear Medicine and Biology
Volume26
Issue number1
DOIs
StatePublished - Jan 1 1999

Keywords

  • Antibody engineering
  • Colon carcinoma xenografts
  • Isoelectric point
  • Radioimmunodiagnosis
  • Single chain fragments

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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