当前位置： SCI文献检索 > CANCER LETTERS期刊下所有文献 > A tandem scFv-based fusion protein and its enediyne-energized analogue show intensified therapeutic efficacy against lung carcinoma xenograft in athymic mice.

A tandem scFv-based fusion protein and its enediyne-energized analogue show intensified therapeutic efficacy against lung carcinoma xenograft in athymic mice.

Abstract：

:Gelatinases play important roles in tumor progression and are abundantly expressed in a variety of malignant tumors. Antibody targeting gelatinases is a possible avenue to fight against cancer. However, antibody alone can not achieve curative efficacy. Herein, we demonstrated the intensified targeting therapy of a tandem scFv-based fusion protein and its enediyne-energized analogue against gelatinases-overexpressed tumor. A fusion protein dFv-LDP, comprising a tandem scFv of anti-gelatinases linked to the apoprotein (LDP) of lidamycin, was generated and showed strong tumor targeting capability in three different tumor xenografts. In PG-BE1 lung carcinoma xenograft, the tumor inhibition rate was 77.5% by dFv-LDP versus 94.2% by dFv-LDP-AE, the product of dFv-LDP assembled with the active enediyne chromophore (AE) of lidamycin. Moreover, the combination of dFv-LDP with dFv-LDP-AE further augmented the therapeutic efficacy, producing initial tumor shrinkage in five of six mice. The microvessel density (P<0.05) and proliferation index (P<0.05) were also stepwise decreased in groups of dFv-LDP, dFv-LDP-AE and the combination. In conclusion, our results demonstrated that the antibody-based therapy against gelatinases was stepwise intensified in use of dFv-LDP, dFv-LDP-AE and dFv-LDP plus dFv-LDP-AE, and indicated that the combination of an antibody with its drug-armed analogue might be of interest as a new approach to augment antitumor efficacy.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Zhong G,Zhang S,Li Y,Liu X,Gao R,Miao Q,Zhen Y

doi

10.1016/j.canlet.2010.02.020

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

124-33

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(10)00121-7

journal_volume

295

pub_type

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