Monoclonal antibody recognizing DKK1/HLA-A2 complex for cancer immunotherapy

 

The invention is a monoclonal antibody directed against the Dickkopf (Dkks) protein. The Dkks family of proteins is a canonical Wnt signaling pathway antagonist which plays varied roles in human physiology and as well as assuming a central role in bone development and formation. As cancer cells, unlike normal cells, express on their surface DKKI peptides/HLA-A2 molecules in HLA-A2+ cancer patients, the inventors synthesized the DKKI peptide P20/HLA-A2 and used it to immunized mice in order to obtain monoclonal antibodies (mAbs) that bind specifically with DKKI -expressing, HLA-A2+ human cancer cells but not HLA-A2+ blood cells or normal tissue cells. These mAbs will have the potential to treat patients with breast, lung, prostate and pancreatic cancers, and myeloma, lymphomas, and leukemia.

 

Stage of Development

 

In vitro data: The antibody has been extensively characterized in in vitro studies, including specificity, surface binding, cytotoxicity, Antibody-dependent cell-mediated cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC) assays.

In vivo data: The inventors are currently conducting in vivo studies in a variety of solid tumors in xenografted mouse models and have demonstrated that this specific antibody kills cancer cells in vitro and in vivo xenografted mouse models.

 

Competitive Landscape

 

While a large number of therapeutic antibodies are being developed for the oncology and represented by blockbuster monoclonal antibody therapeutics such as Avastin and Herceptin, only Novartis and Leap Therapeutics are advancing an antiDKK1 therapeutic. Both companies are currently conducting Phase 2 clinical trials with a DKK1 monoclonal antibody.

 

Competitive Advantages

 

DKK1 is broadly overexpressed by tumor cells including hematological malignancies and solid tumors but absent from most normal tissues, may be an ideal target for immunotherapy.

• VEGF and HER2 are overexpressed in limited cancers. Clinical studies showed that currently approved VEGF-targeting therapies produce initial responses that are followed by a restoration of tumor growth and progression.

 

Patent Information:
Licensing Contact
Joe Jilka
jjilka@houstonmethodist.org

Inventors:
Qing Yi
Jianfei Qian