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Updated: Aug 14, 2026
Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
Antitumor activity of TRAIL recombinant adenovirus in human malignant glioma cells
Ki-Uk Kim1, Su-Yeong Seo, Ki-Young Heo
1Brain Tumor Research, Dong-A University College of Medicine, Busan, Korea.
Abstract:
Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) has been reported to specifically kill malignant cells but to be relatively nontoxic to normal cells. One of disadvantages to previous in vivo protocols was the need for large quantities of TRAIL recombinant protein to suppress tumor growth. To evaluate the antitumor activity and therapeutic value of the TRAIL gene, we constructed adenoviral vectors expressing the human TRAIL gene (Ad.hTRAIL) and transferred them into malignant glioma cells in vitro and tumors in vivo, as an alternative to recombinant soluble TRAIL protein. The results show that TRAIL-sensitive glioma cells infected Ad.hTRAIL undergo apoptosis through the production and expression of TRAIL protein. The in vitro transfer elicited apoptosis, as demonstrated by the quantification of viable or apoptotic cells and by the analysis of cleavage of poly (ADP-ribose) polymerase. Furthermore, in vivo administration of Ad.hTRAIL at the site of tumor implantation suppressed the outgrowth of human glioma xenografts in SCID mice. These results further define Ad.hTRAIL as an anti-tumor therapeutic and demonstrate its potential use as an alternative approach to treatment for malignant glioma.
Insights
Adenoviral vectors delivering the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) gene effectively induce apoptosis in glioma cells. This gene therapy approach shows promise for suppressing malignant glioma tumor growth in vivo.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells.
- Previous TRAIL therapies required high protein doses, limiting in vivo efficacy.
- Malignant gliomas are aggressive tumors with limited treatment options.
Purpose of the Study:
- To evaluate the antitumor activity of adenoviral vectors expressing the human TRAIL gene (Ad.hTRAIL).
- To assess Ad.hTRAIL as an alternative to recombinant TRAIL protein for glioma treatment.
- To investigate the therapeutic potential of gene-delivered TRAIL in malignant glioma.
Main Methods:
- Construction of adenoviral vectors expressing the human TRAIL gene (Ad.hTRAIL).
- In vitro infection of TRAIL-sensitive glioma cells with Ad.hTRAIL.
- In vivo administration of Ad.hTRAIL into human glioma xenografts in SCID mice.
- Assessment of apoptosis via cell counting and poly (ADP-ribose) polymerase cleavage analysis.
Main Results:
- Ad.hTRAIL infection induced apoptosis in glioma cells through TRAIL protein production.
- In vitro studies confirmed apoptosis induction and cell death.
- In vivo administration of Ad.hTRAIL suppressed the growth of human glioma xenografts.
- Successful gene transfer led to TRAIL expression and subsequent tumor suppression.
Conclusions:
- Ad.hTRAIL is an effective agent for inducing apoptosis in malignant glioma cells.
- Adenoviral TRAIL gene therapy presents a viable alternative to recombinant TRAIL protein.
- Ad.hTRAIL demonstrates significant potential as an anti-tumor therapeutic for malignant glioma.
