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

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Single-Chain Antibodies
Angiotensin II
Fusion reactions
Monoclonal Antibodies
Tumors
Neoplasms
Angiotensin Type 1 Receptor
Norepinephrine
Animals
Kinetics
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49. / Wittel, Uwe A.; Jain, Maneesh; Goel, Apollina; Baranowska-Kortylewicz, Janina; Kurizaki, Takashi; Chauhan, Subhash C.; Agrawal, Devendra K.; Colcher, David; Batra, Surinder K.

In: Biochemical and Biophysical Research Communications, Vol. 329, No. 1, 01.04.2005, p. 168-176.

Research output: Contribution to journalArticle

Wittel, Uwe A. ; Jain, Maneesh ; Goel, Apollina ; Baranowska-Kortylewicz, Janina ; Kurizaki, Takashi ; Chauhan, Subhash C. ; Agrawal, Devendra K. ; Colcher, David ; Batra, Surinder K. / Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 329, No. 1. pp. 168-176.
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