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

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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 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 (US)
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

Keywords

Angiotensin II
Antibody engineering
Cancer therapy
Fusion protein
Radioimmunotherapy
scFv

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2005.01.101

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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

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

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

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.",

keywords = "Angiotensin II, Antibody engineering, Cancer therapy, Fusion protein, Radioimmunotherapy, scFv",

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

note = "Funding Information: This study was supported, in part, by a grant from the National Institutes of Health to J.B. (P50 CA72712) and the US Department of Energy (DE-FG02-95ER62024) to S.K.B. ",

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AU - Wittel, Uwe A.

AU - Jain, Maneesh

AU - Goel, Apollina

AU - Baranowska-Kortylewicz, Janina

AU - Kurizaki, Takashi

AU - Chauhan, Subhash C.

AU - Agrawal, Devendra K.

AU - Colcher, David

AU - Batra, Surinder K.

N1 - Funding Information: This study was supported, in part, by a grant from the National Institutes of Health to J.B. (P50 CA72712) and the US Department of Energy (DE-FG02-95ER62024) to S.K.B.

PY - 2005/4/1

Y1 - 2005/4/1

N2 - 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.

AB - 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.

KW - Angiotensin II

KW - Antibody engineering

KW - Cancer therapy

KW - Fusion protein

KW - Radioimmunotherapy

KW - scFv

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

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