Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49

Uwe A. Wittel, Maneesh Jain, Apollina Goel, Janina Baranowska-Kortylewicz, Takashi Kurizaki, Subhash C. Chauhan, Devendra K. Agrawal, David Colcher, Surinder K. Batra

Research output: Contribution to journalArticle

12 Scopus citations


For the therapy of solid tumors, co-administration of angiotensin II (AngII) results in an increased uptake of drugs into the tumor interstitium. We have engineered a dimeric sc(Fv)2-AngII fusion construct that combines the superior kinetics of covalent dimeric scFvs [sc(Fv)2], recognizing the pancarcinoma tumor-associated antigen 72 (TAG-72), with the advantageous intrinsic activity of AngII. The binding characteristics of the fusion construct were unaltered by the addition of the AngII sequence [affinity constant KA 1.18 × 107 and 8.42 × 10 6 M-1 for sc(Fv)2 and sc(Fv)2-AngII, respectively]. The binding of the fusion construct to the angiotensin receptor (AT1) was similar to AngII, and the arterial contraction was 16 ± 1% of the response observed with norepinephrine. In animal studies, the radiolabeled sc(Fv)2-AngII construct exhibited similar uptake and a more homogeneous distribution within the tumor as compared to sc(Fv) 2.

Original languageEnglish (US)
Pages (from-to)168-176
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Apr 1 2005



  • Angiotensin II
  • Antibody engineering
  • Cancer therapy
  • Fusion protein
  • Radioimmunotherapy
  • scFv

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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