October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
Cytolethal distending toxin B from Haemophilus ducreyi delivered by anthrax toxin fusion proteins inhibit tumor cell growth
| Wednesday, November 06, 2013 — Poster Session I | |||
|---|---|---|---|
4:00 p.m. – 6:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIAID |
MOLBIO-3 |
Authors
- C.H. Bachran
- R. Hasikova
- S. Liu
- S.H. Leppla
Abstract
Cytolethal distending toxin (Cdt) is an exotoxin produced by several Gram-negative bacterial species. It is composed of three subunits, CdtA, CdtB, and CdtC, with CdtB being the catalytic subunit. CdtB has been described as a DNase that induces double strand breaks in DNA. We fused CdtB from Haemophilus ducreyi with the N-terminal 254 amino acids of Bacillus anthracis toxin lethal factor (LFn) to achieve uptake into a variety of tumor cells. CdtB is transported into the cytosol of targeted cells via the efficient delivery mechanism of anthrax toxin. The fusion protein efficiently killed various human tumor cell lines by inducing a complete cell cycle arrest in the G2/M phase and subsequently inducing apoptosis. Animal studies showed very low toxicity of a systemically-applied tumor-specific treatment and impressive anti-tumor effects, resulting in a 90% cure rate. This study demonstrates the great potential of a combination of efficient drug delivery by a modified anthrax toxin system and the enzymatic activity of CdtB, and argues for the continued development of this novel anti-cancer drug.
