Methods of Treating Cancer using iNOS-inhibitory Compositions

Description of Invention

 

This technology is a combination therapy using N-Monomethyl-L-arginine (L-NMMA), a small inhibitory molecule against nitric oxide signaling (a driver of tumor-mediated immunosuppression ), with other chemotherapeutics and immunotherapies to overcome treatment resistance in triple negative breast cancer (TNBC) and other cancers including melanoma and head and neck cancer.

 

Stage of Development

 

In vitro data: Nitric Oxide Synthase (iNOS) protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome to be associated with worse prognosis by gene expression as well as immunohistochemical analysis.  L-NMMA inhibitors diminished cell proliferation, migration, and mammosphere formation in TNBC cell lines.

 

In vivo data: L-NMMA was found to reduce tumor growth, lung metastases, tumor initiation, and self-renewal in TNBC patient-derived xenografts.  Furthermore, L-NMMA in combination with docetaxel significantly, inhibited in vivo tumor growth compared with docetaxel alone in TNBC xenograft models.

 

Clinical data: Based on these findings, an ongoing Phase Ib/II clinical trial of L-NMMA in combination with docetaxel in patients with refractory locally advanced or metastatic TNBC is underway (NCT02834403).

 

Competitive Landscape

 

TNBC is an aggressive form of breast cancer with higher risk of metastasis and tumor relapse, with no effective targeted therapy.  TNBC is not responsive to hormone therapy nor HER2 drugs and response to chemotherapy is short-lived with inevitable resistance.  iNOS is a potential target since it is highly expressed in various cancers and has been associated with poor prognosis in invasive TNBC.  L-NMMA, an inhibitor or iNOS, is an attractive therapeutic for a patient group with unmet needs.

 

Competitive Advantages

 

•       Promising therapeutic with a targeted mechanism

•       Overcomes chemotherapeutic resistance

•       Overcomes metastasis

•       Combination therapy with various chemotherapeutics or immunomodulators

•       Provides alternative therapeutics where few options are available

•       Safety studies are well tolerated

 

Intellectual Property

 

US Issued Patent 10,420,838 on September 24, 2019

PCT Filed April 8th, 2015 and further national filings

 

Breast Cancer Res. 2015; 17(1): 25.

 

Patent Information:
Licensing Contact
Belisa Diaz
bdiaz@houstonmethodist.org

Inventors:
Jenny Chang