Therapeutic expression of an anti-death receptor 5 single-chain fixed-variable region prevents tumor growth in mice.

نویسندگان

  • Juan Shi
  • Yanxin Liu
  • Yong Zheng
  • Yabin Guo
  • Jinchun Zhang
  • Pik-To Cheung
  • Ruian Xu
  • Dexian Zheng
چکیده

The clinical use of the single-chain fixed-variable (scFv) fragments of recombinant monoclonal antibodies as credible alternatives for classic therapeutic antibodies has two limitations: rapid blood clearance and inefficient local expression of functional molecules. In attempt to address these issues, we have developed a novel gene therapy protocol in which the anti-death receptor 5 (DR5) scFv fragments were either in vitro expressed in several tumor cell lines, or in vivo expressed in mice, using recombinant adeno-associated virus (rAAV)-mediated gene transfer. Viral transduction using the rAAV-S3C construct, which encodes a scFv molecule (S3C scFv) specific to DR5, led to stable expression in tumor cell lines and showed apoptosis-inducing activity in vitro, which could be inhibited by recombinant DR5 but not by DR4. A single i.m. injection of rAAV-S3C virus in nude mice resulted in stable expression of DR5-binding S3C scFv proteins in mouse sera for at least 240 days. Moreover, the expression of S3C scFv was associated with significant suppression of tumor growth and the increase of tumor cell apoptosis in previously established s.c. human lung LTEP-sml and liver Hep3B tumor xenografts.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Cloning and Expression of the Variable Regions of Anti-EGFR Monoclonal Antibody in E. coli for Production of a Single Chain Antibody

Background:Epidermal growth factor receptor (EGFR) overexpression is a characteristic of several malignancies and could be considered as an excellent target for designing specific inhibitors such as anti-EGFR monoclonal antibodies for cancer therapy. Drawbacks exerted by large sizes of full-length antibodies have lead to the development of single chain antibodies, which benefit from having smal...

متن کامل

Design and Construction of a Novel Humanized Single-Chain Variable-Fragment Antibody against the Tumor Necrosis Factor alpha

The pro-inflammatory cytokine, TNF-α, which plays a major role in the development and persistence of inflammatory diseases, is the basis for the use of anti-TNF-α therapies. The neutralization of TNF-α or blockage of its binding to the corresponding receptor has mainly served as a therapeutic strategy against some diseases. This study aimed to investigate the production of a humanized single ch...

متن کامل

Design and Construction of a Novel Humanized Single-Chain Variable-Fragment Antibody against the Tumor Necrosis Factor alpha

The pro-inflammatory cytokine, TNF-α, which plays a major role in the development and persistence of inflammatory diseases, is the basis for the use of anti-TNF-α therapies. The neutralization of TNF-α or blockage of its binding to the corresponding receptor has mainly served as a therapeutic strategy against some diseases. This study aimed to investigate the production of a humanized single ch...

متن کامل

Triple tandem mimotope peptide of Epidermal Growth Factor Receptor displaying on the surface of M13 phage induces anti-tumor response in mice tumor model

Introduction: Epidermal growth factor receptor (EGFR) has been shown to play a critical role in tumor cell growth and its overexpression has been observed in many epithelial tumors. In the field of cancer vaccine research, displaying the peptide mimotope on the surface of phage particles has shown promising results. Methods: In this study using m13-PVIII phage display system, two constructs we...

متن کامل

Anti-tumor Effect of Ginkgo biloba Exocarp Extracts on B16 Melanoma Bearing Mice Involving P I3K/Akt/HIF-1α/VEGF Signaling Pathways

The objective of this study is to investigate the anti-tumor effect of Ginkgo biloba exocarp extracts (GBEE) on B16 melanoma bearing mice and its related molecular mechanisms. The B16-F10 melanoma solid tumor model was established in C57BL/6J mice. The tumor-bearing mice were treated with GBEE (50, 100, 200 mg/kg), taking cis-Dichlorodiamineplatinum (Ⅱ) (DDP, 3 mg/kg) as pos...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 66 24  شماره 

صفحات  -

تاریخ انتشار 2006