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Published on: May 6, 2015
Adeno-associated virus-mediated anti-DR5 chimeric antibody expression suppresses human tumor growth in nude mice
Fujia Lv1, Yuhe Qiu, Yaxi Zhang
1National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Abstract:
In the present study we demonstrate that adeno-associated virus (AAV)-mediated anti-DR5 (death receptor 5) mouse-human chimeric antibody (shorten as Adximab) expression significantly suppressed tumor cell growth by inducing apoptosis both in vitro and in vivo. The viral-expressed and cell-secreted Adximab efficiently bound DR5 with an affinity of 0.7nM and induced apoptosis of various tumor cells, but not normal cells. A single intramuscular injection of recombinant AAV particles resulted in a stable expression of Adximab in mouse serum for at least 70days. AAV-mediated Adximab expression led to a significant suppression of tumor growth in nude mice receiving xenografts of human liver and colon cancer. These data suggest that chimeric antibody gene transfer may provide an alternative strategy for the therapy of varieties of cancers.
Insights
Adeno-associated virus (AAV)-mediated expression of anti-death receptor 5 (DR5) chimeric antibody suppressed tumor growth by inducing apoptosis. This gene therapy approach shows promise for treating various cancers.
Area of Science:
- Oncology
- Gene Therapy
- Immunology
Background:
- Cancer therapy often faces challenges with efficacy and specificity.
- Targeting death receptor 5 (DR5) is a strategy to induce cancer cell apoptosis.
- Gene transfer offers a novel approach for therapeutic protein delivery.
Purpose of the Study:
- To evaluate the efficacy of adeno-associated virus (AAV)-mediated expression of an anti-DR5 chimeric antibody (Adximab) for cancer treatment.
- To assess the in vitro and in vivo anti-tumor activity of Adximab.
- To determine the stability and safety of AAV-mediated gene transfer for antibody production.
Main Methods:
- AAV vector construction for Adximab expression.
- In vitro assessment of Adximab binding to DR5 and induction of apoptosis in tumor cells.
- In vivo studies using xenograft models of human liver and colon cancer in nude mice.
- Monitoring of Adximab serum levels post-injection.
Main Results:
- AAV-mediated Adximab expression effectively suppressed tumor cell growth and induced apoptosis in vitro and in vivo.
- Adximab demonstrated high affinity binding to DR5 (0.7nM) and selectively targeted cancer cells.
- Stable Adximab expression was achieved in mouse serum for over 70 days.
- Significant tumor growth suppression was observed in liver and colon cancer xenograft models.
Conclusions:
- AAV-mediated gene transfer of chimeric antibodies targeting DR5 is a feasible and effective anti-cancer strategy.
- Adximab shows potential as a therapeutic agent for various cancers by selectively inducing apoptosis.
- Chimeric antibody gene therapy represents a promising alternative for cancer treatment.
