Potent Systemic Anticancer Activity of Adenovirally Expressed EGFR-Selective TRAIL Fusion ProteinBremer, E., van Dam, G. M., de Bruyn, M., van Riezen, M., Dijkstra, M., Kamps, G., Helfrich, W. & Haisma, H., Dec-2008, In : Molecular Therapy. 16, 12, p. 1919-1926 8 p.
Research output: Contribution to journal › Article › Academic › peer-review
- Groningen University Institute for Drug Exploration (GUIDE)
- Faculty of Medical Sciences
- Groningen Research Institute of Pharmacy
- Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Targeted Gynaecologic Oncology (TARGON)
- Translational Immunology Groningen (TRIGR)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Stem Cell Aging Leukemia and Lymphoma (SALL)
Previously, we demonstrated potent tumor cell-selective pro-apoptotic activity of scFv425:sTRAIL, a recombinant fusion protein comprised of EGFR-directed antibody fragment (scFv425) genetically fused to human soluble TNF-related apoptosis-inducing ligand (sTRAIL). Here, we report on the promising therapeutic systemic tumoricidal activity of scFv425:sTRAIL when produced by the replication-deficient adenovirus Ad-scFv425:sTRAIL. In vitro treatment of EGFR-positive tumor cells with Ad-scFv425:sTRAIL resulted in the potent induction of apoptosis of not only infected tumor cells, but importantly also of up to 60% of noninfected EGFR-positive tumor cells. A single intraocular injection of Ad-scFv425:sTRAIL in tumor-free nu/nu mice resulted in predominant liver infection and concomitant high blood plasma levels of scFv425:sTRAIL. These mice showed no sign of Ad-scFv425:sTRAIL-related liver toxicity. Identical treatment of mice with established intraperitoneal renal cell carcinoma xenografts resulted in rapid and massive tumor load reduction and subsequent long-term survival. Taken together, adenoviral-mediated in vivo production of scFv425:sTRAIL may be exploitable for systemic treatment of EGFR-positive cancer.
|Number of pages||8|
|Publication status||Published - Dec-2008|
- VIRUS THYMIDINE KINASE, APOPTOSIS INDUCTION, MEDIATED APOPTOSIS, GENE-TRANSFER, LIGAND, VECTORS, CELLS, SPECIFICITY, THERAPY, RECEPTOR