Microfibrillar-associated Protein 5 (MFAP5)-Specific Monoclonal Antibodies as Therapeutic Agents in Ovarian and Pancreatic Cancers

Description of Invention

 

The invention are therapeutic monoclonal antibodies directed against microfibrillar-associated fibroblast-derived secreted protein 5 (MFAP-5) for the treatment of ovarian and pancreatic cancer.  Cancer associated fibroblasts (CAFs) in the tumor stromal microenvironment exhibit altered secretion of extracellular proteins, which modify the tumor environment and promote cancer cell proliferation, migration, and invasion.  MFAP-5 has been shown to be up regulated in CAF of multiple tumor types and is associated with poor prognosis.

 

Stage of Development

 

In vitro data: Monoclonal antibodies were developed using human MFAP5 recombinant protein as an antigen and antibodies from hybridoma clones were evaluated for their specificity to human and murine MFAP5.  The kinetics of binding affinity and the specificity of the antibody clones were determined and was followed by epitope mapping and functional characterization.

In vivo data: One antibody clone, recognizing a common epitope shared between human and murine MFAP5 protein, were further selected for in vivo studies. Results showed that this clone down-regulated MFAP5-induced collagen production in cancer associated fibroblasts, suppressed intratumoral microvessel leakiness, and enhanced paclitaxel bioavailability in both ovarian and pancreatic cancer mouse models.

 

Competitive Landscape

 

Despite the advances to date in antibody-based therapeutics, the efficacy of targeting CAF-derived antigens by MAbs in cancer treatment has not been explored.  The identification of agents that inhibit MFAP5 would be of benefit in expanding the number of therapeutic options. The present invention provides new antibody therapeutics for use in anti-fibrosis and anti-tumor therapy particularly in ovarian and pancreatic cancers.

 

Competitive Advantages

 

•       Antibodies with high affinity and specificity

•       Inhibits tumor progression

•       Inhibits fibrosis

•       Induces tumor vessel normalization

•       Enhances chemosensitivity in ovarian and pancreatic cancer

•       No cytotoxic effects

 

Intellectual Property

 

Provisional Patent Application filed; July 22, 2019

 

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

Inventors:
Stephen Wong
Jianting Sheng
Tsz Lun Yeung
Sze Lee Cecilia Leung
Samuel Mok