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Gene therapy with apoptin induces regression of xenografted human hepatomas
Marjolijn M van der Eb1, Alexandra M Pietersen, Frank M Speetjens
1Department of Molecular Cell Biology, Leiden University Medical Centre, The Netherlands.
Abstract:
The chicken anemia virus-derived Apoptin protein shows remarkable specificity; namely, it induces apoptosis in tumor cells, but not in normal diploid cells. We have exploited the Apoptin gene for use in cancer gene therapy. Here we demonstrate that adenovirus-mediated intratumoral transfer and expression of the Apoptin gene results in regression or complete remission of human hepatomas grown as xenografts in immune-deficient mice, and significantly increases their survival long term. Early after intratumoral injection, Apoptin could be detected in significant quantities by Western blot analyses and immunohistochemistry. Furthermore, cell death and disruption of the tumor integrity were apparent in the transduced regions. This experimental gene therapeutic strategy constitutes a unique example of specific antitumor activity using a virus-derived gene with broad-spectrum applicability.
Insights
Apoptin, a gene from chicken anemia virus, specifically targets tumor cells for apoptosis. Adenovirus-mediated gene transfer of Apoptin led to significant tumor regression and improved survival in hepatoma xenografts.
Area of Science:
- Oncology
- Gene Therapy
- Virology
Background:
- Apoptin protein, derived from chicken anemia virus, selectively induces apoptosis in tumor cells.
- This specificity makes Apoptin a promising candidate for cancer gene therapy applications.
Purpose of the Study:
- To investigate the efficacy of adenovirus-mediated intratumoral transfer of the Apoptin gene in treating human hepatomas.
- To evaluate the impact of Apoptin gene therapy on tumor regression, remission, and long-term survival in a xenograft model.
Main Methods:
- Adenovirus-mediated intratumoral delivery of the Apoptin gene into human hepatoma xenografts in immune-deficient mice.
- Detection of Apoptin expression using Western blot and immunohistochemistry.
- Assessment of tumor integrity and cell death in transduced regions.
Main Results:
- Intratumoral Apoptin gene expression resulted in significant tumor regression and complete remission.
- Apoptin gene therapy significantly increased long-term survival rates in treated mice.
- Early detection of Apoptin confirmed successful gene transfer, with observed cell death and disrupted tumor integrity.
Conclusions:
- Adenovirus-mediated Apoptin gene therapy demonstrates specific antitumor activity against human hepatomas.
- This approach offers a promising, broad-spectrum gene therapeutic strategy for various cancers.
- Apoptin's tumor-specific apoptosis-inducing properties hold significant potential for future cancer treatments.