TRAIL stabilization and cancer cell sensitization to its proapoptotic activity achieved through genetic fusion with arginine deiminase

16Citations
Citations of this article
18Readers
Mendeley users who have this article in their library.

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) binds to death receptors and induces apoptosis in various cancer cell lines while sparing normal cells. Recombinant TRAIL has shown good safety and efficacy profiles in preclinical cancer models. However, clinical success has been limited due to poor PK and development of resistance to death receptor-induced apoptosis. We have addressed these issues by creating a fusion protein of TRAIL and arginine deiminase (ADI). The fusion protein benefits from structural and functional synergies between its two components and has an extended half-life in vivo. ADI downregulates survivin, upregulates DR5 receptor and sensitizes cancer cells to TRAIL induced apoptosis. ADI-TRAIL fusion protein was efficacious in a number of cell lines and synergized with some standard of care drugs. In an HCT116 xenograft model ADI-TRAIL localized to the tumor and induced dose-dependent tumor regression, the fusion protein was superior to rhTRAIL administered at the same molar amounts.

References Powered by Scopus

This article is free to access.

Get full text
2063Citations
373Readers

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Brin, E., Wu, K., Dagostino, E., Kuo, M. M. C., He, Y., Shia, W. J., … Thomson, J. (2018). TRAIL stabilization and cancer cell sensitization to its proapoptotic activity achieved through genetic fusion with arginine deiminase. Oncotarget, 9(97), 36914–36928. https://doi.org/10.18632/oncotarget.26398

Readers over time

‘19‘20‘21‘22‘23‘2402468

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 6

86%

Researcher 1

14%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 5

63%

Neuroscience 1

13%

Agricultural and Biological Sciences 1

13%

Medicine and Dentistry 1

13%

Save time finding and organizing research with Mendeley

Sign up for free
0