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- Title
Selective proapoptotic activity of a secreted recombinant antibody/AIF fusion protein in carcinomas overexpressing HER2.
- Authors
Yu, C. -J.; Jia, L. -T.; Meng, Y. -L.; Zhao, J.; Zhang, Y.; Qiu, X. -C.; Xu, Y. -M.; Wen, W. -H.; Yao, L. -B.; Fan, D.-M.; Jin, B. -Q.; Chen, S. -Y.; Yang, A. -G.
- Abstract
Apoptosis-inducing factor (AIF) represents a caspase-independent apoptotic pathway in the cell, and a mitochondrial localization sequence-truncated AIF (AIFΔ1–120) can be relocated from the cytoplasm to the nucleus and exhibit a constitutive proapoptotic activity. Here, we generated a chimeric immuno-AIF protein, which comprised an HER2 antibody, a Pseudomonas exotoxin translocation domain and AIFΔ1–120. Human Jurkat cells transfected with the immuno-AIF gene could express and secrete the chimeric protein, which selectively recognized HER2-overexpressing tumor cells and was endocytosed. Subsequent cleavage of truncated AIF from immuno-AIF and its release from the internalized vesicles resulted in apoptosis of tumor cells. Intramuscular injection of the immuno-AIF gene caused significant suppression of tumors and substantially prolonged mice survival in an HER2-overexpressing xenograft tumor model. Our study demonstrates the feasibility of the immuno-AIF gene as a novel approach to treating cancers that overexpress HER2.Gene Therapy (2006) 13, 313–320. doi:10.1038/sj.gt.3302672; published online 3 November 2005
- Subjects
APOPTOSIS; CELL death; MITOCHONDRIA; ORGANELLES; CYTOPLASM; PSEUDOMONAS; ENDOCYTOSIS; CELL physiology; GENE therapy; GENETIC engineering
- Publication
Gene Therapy, 2006, Vol 13, Issue 4, p313
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302672