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

doi:10.1016/j.bbrc.2005.01.101

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

Department of Clinical and Translational Science

Research output: Contribution to journal › Article

12 Scopus citations

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 K_A 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 language	English
Pages (from-to)	168-176
Number of pages	9
Journal	Biochemical and Biophysical Research Communications
Volume	329
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2005.01.101
State	Published - 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

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 journal › Article

Wittel, UA, Jain, M, Goel, A, Baranowska-Kortylewicz, J, Kurizaki, T, Chauhan, SC, Agrawal, DK, Colcher, D & Batra, SK 2005, 'Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49', Biochemical and Biophysical Research Communications, vol. 329, no. 1, pp. 168-176. https://doi.org/10.1016/j.bbrc.2005.01.101

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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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.",

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