Selectively targeting cancer cells sparing the normal organs is a major challenge in oncology drug discovery. Paramount efforts are continuously made to find new anticancer agents that can reduce the physical toll associated with cancer treatment. Scientists at the University of Virginia School of Medicine discovered a new link between cancer cells and developing oocytes, the original cell from which all the tissues in the body derive, that could become a frontline treatment for women who have cancers of many types and want to preserve fertility.
While working on new methods of contraception, the group headed by Professor John C. Herr discovered a surprising link between developing eggs and tumor cells. Both cell types express on their surface the SAS1B protein also know as ovastacin. Ovastacin is stored within small granules under the surface of developing oocytes and is externalized after fertilization to degrade other surface proteins on the oocytes membrane that promote sperm recognition and docking. Ovastacin degrading activity prevents more than one sperm from binding to and fertilizing the oocyte (polyspermia). Cancer cells have evolved to take advantage of ovastacin degrading activity to make their way through surrounding tissues, leave their primary site and give rise to metastasis. Professor Herr and coworker, by analyzing the National Cancer Institute's GenBank database, found out that SAS1B expression is a rather common feature for cancer cells, as it is present in uterine, breast, melanoma, renal, ovarian, head and neck, and pancreatic cancers. There is also evidence to suggest that it appears in bladder cancers.
However, beside the small group of growing eggs in the ovary, the SAS1B protein is virtually absent in other tissues in the body, making it the ideal candidate for targeted therapy.
Cancer-oocyte neoantigen
Because of its exclusive presence on developing eggs and cancer cells, ovastatin can be used as a target for newly devised anticancer molecules made of antibodies, capable of recognizing SAS1B, conjugated with a toxin. The antibody-toxin conjugate is rapidly internalized by SAS1B expressing cells and is capable of killing them within few days.
Amazingly, while the antibodies attack the pool of growing egg cells in addition to the SAS1B positive cancer cells, the ovaries' supply of dormant eggs, that typically don’t express ovastatin, are spared by this treatment and once the drug course is completed oocytes are able to develop and ovulate again within a short period of time.
Crown Bioscience congratulates the team of researcher from University of Virginia on their discovery and looks forward to following the development of this new immunotherapy in the clinic. At Crown we have developed industry-leading fully integrated drug discovery capabilities to increase the speed and efficiency of progressing hits to preclinical candidates. Our disease expertise and unique translational research platforms translate into successful identification of our client’s most robust molecules, strategic therapeutic area and indications, and more successful Phase II & III clinical trials.
Our unique collection of cancer models (HuPrime®), assays, and annotated databases (HuBase™) can be used by our clients to select clinical candidates and improve preparation for clinical development by identifying biomarkers for patient responders, leveraging the curated knowledge of our extensive model collection to identify genetic signatures – HuSignature™. Alternatively we can take your motif or “fingerprint” which characterizes patient responders and non-responders to select models to act as human surrogates in a Phase II-like or “Avatar” trial – HuTrial™
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