A New Anti-triple Negative Breast Cancer Agent

Background:

Approximately 10-15% of all breast cancers are triple negative, lacking the estrogen or progesterone receptors and the human epidermal growth factor receptor 2 (HER2).  TNBC is an aggressive form of cancer with a poorer prognosis than the other breast cancers.  Annually in the U.S. there are 311,000 new invasive breast cancer cases and 42,000 deaths.  The bottom line is 13% of American women will develop breast cancer sometime in their lifetime.

Technology Overview:

Type II heat-labile LT-IIc enterotoxin is a natural product produced by Escherichia coli.  It consists of one A polypeptide with ADP-ribosyltransferase activity and five B polypeptides which bind glycoconjugates of the host.  LT-IIc is cytotoxic towards triple-negative breast cancer (TNBC) cells but not normal cells.  The B subunits bind to cell surface gangliosides.  The molecule constructed at University at Buffalo retains glycoside binding, removes the ADP-ribosylation ability while maintaining cytotoxicity.  Targeting of these gangliosides by modified LT-IIc or human monoclonal antibodies would be useful for treating TNBC.

Advantages:

• Non-toxic to cells other than to TNBC cells
• Novel pathway

Applications:

• Direct treatment of triple-negative breast cancer patients
• Drug discovery tool

Intellectual Property Summary:

U.S. Provisional patent application 63/670,560 was filed on July 12, 2024.

Stage of Development:

• In vitro cell culture tested

https://en.wikipedia.org/wiki/Technology_readiness_level

Licensing Status:

Available for license or collaboration.

Licensing Potential:

Exclusive for drug development, non-exclusive as a research tool.

Additional Information:

Toxins publication abstract