Production and radioimmunoimaging of novel fully human phage display recombinant antibodies and growth inhibition of lung adenocarcinoma cell line overexpressing Prx I
Production and radioimmunoimaging of novel fully human phage display recombinant antibodies and growth inhibition of lung adenocarcinoma cell line overexpressing Prx I
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新型全人噬菌体展示重组抗体的生产和放射免疫成像以及过表达 Prx I 的肺腺癌细胞系的生长抑制
DOI：
10.4161/cbt.8.14.8727
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发表时间：
2009-07
影响因子：
3.6
通讯作者：
Li, Shaolin
中科院分区：
文献类型：
--
作者：
Luo, Yi;Pang, Hua;Li, Shujie;Cao, Hui;Peng, Zhiping;Fan, Chunbo;Li, Shaolin
The Peroxiredoxin I (Prx I) is a member of the Peroxiredoxin family, which is overexpressed in many diverse tumor types and is an anti-apoptosis protein for tumor cell proliferation and survival. Therapeutic strategies targeting the Prx I may therefore be effective broad-spectrum anticancer agents. We construct a phage display single-chain variable fragment (scFv) antibody library and sieve out the fully human, lung adenocarcinoma-sepcific monoclonal antibodies. The selection on Prx I was performed using above-mentioned lung adenocarcinoma-sepcific monoclonal antibodies with high affinity to Prx I overexpressing lung adenocarcinoma cells. The candidate scFv sequences, based on enzyme-linked immunosorbent assay (ELISA) screening data, were chosen for soluble expression, and a 30 kDa band was observed on polyacrylamide gel electrophoresis as predicted. The purified antibodies were characterized by immunoblotting and showed high specificity to Prx I-overexpressing lung adenocarcinoma cells A549. Radioimmunoimaging was taken to evaluate specificity and distribution of antibodies in vivo. The radiolocalization index (RI) of tumor/serum and tumor/muscle gradually increased, reaching its peak (4.06±0.13 and 5.17±0.97, respectively) at 48 h postadministration. Single photon emission computed tomography (SPECT) imaging showed the radioactivity was aggregated in tumor locations and tumor imaging was clearly observed. The internalized scFv resulted in antibody-mediated cell apoptosis and down regulation of Prx I expression. These results demonstrate that the scFv possesses strong antitumor activity on lung adenocarcinoma and may therefore be an effective therapeutic candidate for the treatment of cancers that are dependent on Prx I for growth and survival.
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影响因子：
3.9
作者：
L. Weiner
通讯作者：
L. Weiner
影响因子：
2
作者：
Y. M. Chung;Y. Yoo;J. K. Park;Y. T. Kim;H. Kim
通讯作者：
Y. M. Chung;Y. Yoo;J. K. Park;Y. T. Kim;H. Kim
影响因子：
17.3
作者：
Hoogenboom, HR
通讯作者：
Hoogenboom, HR
影响因子：
3.1
作者：
Yoshiko Kita;Julia Tseng;Tom Horan;Jie Wen;J. Philo;David Chang;B. Ratzkin;Robert E. Pacifici;D. Brankow;Sylvia Hu;Yi Luo;Duanzhi Wen;Tsutomu Arakawa;Margery Nicolson
通讯作者：
Yoshiko Kita;Julia Tseng;Tom Horan;Jie Wen;J. Philo;David Chang;B. Ratzkin;Robert E. Pacifici;D. Brankow;Sylvia Hu;Yi Luo;Duanzhi Wen;Tsutomu Arakawa;Margery Nicolson
影响因子：
9.7
作者：
Toru Yanagawa;Satoshi Iwasa;T. Ishii;Katsuhiko Tabuchi;H. Yusa;K. Onizawa;Ken Omura;Hiroyuki Harada;Haruhiko Suzuki;Hiroshi Yoshida
通讯作者：
Toru Yanagawa;Satoshi Iwasa;T. Ishii;Katsuhiko Tabuchi;H. Yusa;K. Onizawa;Ken Omura;Hiroyuki Harada;Haruhiko Suzuki;Hiroshi Yoshida