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

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Abstract

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
Pages (from-to)168-176
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume329
Issue number1
DOIs
StatePublished - Apr 1 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Wittel, U. A., Jain, M., Goel, A., Baranowska-Kortylewicz, J., Kurizaki, T., Chauhan, S. C., Agrawal, D. K., Colcher, D., & Batra, S. K. (2005). Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49. Biochemical and Biophysical Research Communications, 329(1), 168-176. https://doi.org/10.1016/j.bbrc.2005.01.101