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 language | English |
|---|---|
| Pages (from-to) | 168-176 |
| Number of pages | 9 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 329 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 1 2005 |
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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 journal › Article
}
TY - JOUR
T1 - Engineering and characterization of a divalent single-chain Fv angiotensin II fusion construct of the monoclonal antibody CC49
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.
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.
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UR - http://www.scopus.com/inward/citedby.url?scp=13844281694&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2005.01.101
DO - 10.1016/j.bbrc.2005.01.101
M3 - Article
C2 - 15721289
AN - SCOPUS:13844281694
VL - 329
SP - 168
EP - 176
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -