TY - JOUR
T1 - Combined Effects of Tamoxifen and a Chimeric Humanized Single Chain Antibody against the Type I IGF Receptor on Breast Tumor Growth in vivo
AU - Ye, J. J.
AU - Liang, S. J.
AU - Guo, N.
AU - Li, S. L.
AU - Wu, A. M.
AU - Giannini, S.
AU - Sachdev, D.
AU - Yee, D.
AU - Brünner, N.
AU - Ikle, D.
AU - Fujita-Yamaguchi, Y.
PY - 2003/11
Y1 - 2003/11
N2 - Proliferative and anti-apoptotic actions of IGFs are mediated by the IGF-I receptor (IGF-IR), to which both IGF-I and -II bind with high affinity. We previously reported that αIGF-IR scFv-Fc (scFv-Fc) consisting of the αIGF-IR scFv and human IgG1 Fc domain retained general characteristics of the parental 1H7 monoclonal antibody, and significantly suppressed MCF-7 tumor growth. We proposed IGF-IR down-regulation as a possible mechanism for inhibition of MCF-7 tumor growth. To further determine the therapeutic potentials of this approach, in vivo effects of this antibody on breast tumor growth were evaluated in the absence or presence of tamoxifen (Tam) using a T61 human breast tumor model. T61 xenograft growth in athymic mice was compared under five conditions, PBS, scFv-Fc, Tam, scFv-Fc+Tam, and control antibody. While treatment with PBS and control antibody did not affect T61 tumor growth, scFv-Fc, Tam, and scFv-Fc+Tam treatments significantly suppressed the tumor growth during the first two weeks of treatment. Although the growth inhibitory effect of scFv-Fc during the first two weeks was significant, the tumor grew as rapidly as PBS-treated tumors thereafter. This rapid tumor growth was suppressed when scFv-Fc was combined with Tam. Throughout four weeks, the combined Tam+scFv-Fc treatment was more effective in inhibiting the T61 tumor growth than scFv-Fc or Tam treatment alone. scFv-Fc treatment down-regulated IGF-IR which appears to contribute to tumor growth inhibition. This study provides evidence that simultaneous targeting of IGF-IR and the estrogen receptor may enhance the therapeutic effect.
AB - Proliferative and anti-apoptotic actions of IGFs are mediated by the IGF-I receptor (IGF-IR), to which both IGF-I and -II bind with high affinity. We previously reported that αIGF-IR scFv-Fc (scFv-Fc) consisting of the αIGF-IR scFv and human IgG1 Fc domain retained general characteristics of the parental 1H7 monoclonal antibody, and significantly suppressed MCF-7 tumor growth. We proposed IGF-IR down-regulation as a possible mechanism for inhibition of MCF-7 tumor growth. To further determine the therapeutic potentials of this approach, in vivo effects of this antibody on breast tumor growth were evaluated in the absence or presence of tamoxifen (Tam) using a T61 human breast tumor model. T61 xenograft growth in athymic mice was compared under five conditions, PBS, scFv-Fc, Tam, scFv-Fc+Tam, and control antibody. While treatment with PBS and control antibody did not affect T61 tumor growth, scFv-Fc, Tam, and scFv-Fc+Tam treatments significantly suppressed the tumor growth during the first two weeks of treatment. Although the growth inhibitory effect of scFv-Fc during the first two weeks was significant, the tumor grew as rapidly as PBS-treated tumors thereafter. This rapid tumor growth was suppressed when scFv-Fc was combined with Tam. Throughout four weeks, the combined Tam+scFv-Fc treatment was more effective in inhibiting the T61 tumor growth than scFv-Fc or Tam treatment alone. scFv-Fc treatment down-regulated IGF-IR which appears to contribute to tumor growth inhibition. This study provides evidence that simultaneous targeting of IGF-IR and the estrogen receptor may enhance the therapeutic effect.
KW - Breast Tumor Growth
KW - IGF
KW - Inhibition
KW - Recombinant Antibody
KW - Single Chain Antibody
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=0346725863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346725863&partnerID=8YFLogxK
U2 - 10.1055/s-2004-814145
DO - 10.1055/s-2004-814145
M3 - Article
C2 - 14710366
AN - SCOPUS:0346725863
SN - 0018-5043
VL - 35
SP - 836
EP - 842
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
IS - 11-12
ER -