On September 20, 2016 Abilita Bio, Inc. reported that it has been awarded a Phase I Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) to develop therapeutic antibodies targeting G Protein-Coupled Receptors (GPCRs) involved in the metastasis of breast cancer, including prostaglandin E2 receptor 2 (EP2), prostaglandin E2 receptor 4 (EP4), and C-C chemokine receptor 7 (CCR7) (Press release, Abilita Bio, SEP 20, 2016, View Source [SID:SID1234515259]). With an estimated 1.7 million new cases each year, breast cancer is the most common cancer among women worldwide. It is also the leading cause of cancer death among women, taking the lives of over 450,000 annually. In addition to the patients who are diagnosed with metastatic disease at initial diagnosis, nearly 30 percent of women diagnosed with early breast cancer will eventually develop metastatic disease.
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The chemokine receptor CCR7 is highly expressed in human breast cancer cells, malignant breast tumors and metastases, and overexpression correlates with larger primary tumors, deeper lymphatic invasion and poor prognosis. EP2 and EP4 receptors are positively correlated with increased breast cancer metastasis and have been implicated in suppression of the antitumor activity of natural killer cells. Given the body of evidence that implicates CCR7, EP2 and EP4 in cancer metastasis and immunosuppression, targeted inhibitory antibody therapeutics may address unmet needs in breast cancer therapy.
GPCRs have been proven to be challenging targets for antibody discovery due to low cell surface expression, lack of immunogenicity and marginal conformational stability when removed from the membrane. To address these limitations, Abilita Bio will leverage its directed evolution technology to rapidly generate enhanced GPCR antigens called EMPs (Enabled Membrane Proteins) that can be used for discovery and development of therapeutic antibodies targeting CCR7, EP2 and EP4 for the prevention or treatment of metastatic breast cancer.
"Antibody therapeutics against GPCRs have tremendous potential in treating cancer due to their exquisite specificity, high affinity and low toxicity relative to small molecules. However, despite intense efforts to develop them, only one GPCR targeted therapeutic antibody has gained approval in the world," said Mauro Mileni, Ph.D., Abilita Bio’s CEO and principal investigator on this grant. "We expect the use of EMPs as antigens to dramatically increase the probability of discovering new therapeutic antibodies to treat serious diseases, while reducing costs and development timelines."
About GPCRs
G Protein-Coupled Receptors (GPCRs) represent the largest class of membrane proteins in humans, and bind almost all of the known neurotransmitters and hormones that are released synaptically or secreted into the circulatory system. GPCRs are expressed in all tissue types and organs, and are associated with many diseases. The GPCR super-family includes approximately 400 medically relevant targets. To date more than 110 receptors have been exploited as drug targets, while most of the remaining receptors are orphan (130) or under-characterized.