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

Biochemical and Biophysical Research Communications
Uwe A WittelSurinder K Batra

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 x 10(7) and 8.42 x 10(6) M(-1) for sc(Fv)(2) and sc(Fv)(2)-AngII, respectively]. The binding of the fusion construct to the angiotensin receptor (AT(1)) 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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Citations

Sep 27, 2006·Cancer Biotherapy & Radiopharmaceuticals·Huguette Albrecht, Sally J DeNardo
Mar 27, 2010·Journal of Biomedicine & Biotechnology·Qiang TongGuo-Bin Wang
May 22, 2007·Trends in Biotechnology·Maneesh JainSurinder K Batra
Jan 9, 2019·Cancer Metastasis Reviews·Rakesh BhatiaSurinder K Batra
Nov 28, 2006·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Feb 21, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maneesh JainSurinder K Batra

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