Ovarian cancer is the first therapeutic area for the Company's discovery platform This project is pursuing a discovery path similar to that used to develop Herceptin, a hugely successful mAb therapeutic for breast cancer and specifically targeted to those patients that are positive for the up- regulation of the marker Her2neu. As with Herceptin, the Company is immunizing mice with whole cancer cells (lines) to generate the antibodies. In the OC project, researchers used four distinct ovarian cancer cell line-- representing two of the most common forms of OC--as the immunogen.
The initial screen, using immunofluorescent microscopy (IFM) and ELISA, involves identifying those antibodies that are binding to cancer cell lines but otherwise do not attach to normal, non-cancerous control cells (click here to view images). Once positives are identified, priority is given to those mAbs showing reactivity on two or more of the four OC cell lines and negative on the control cell line, and to those that are IgG isotypes. Since Abeome is working with mouse antibodies, and a successful therapeutic will require humanization, the Company is selectively moving a few interesting IgMs through our screening process. Antibodies that continue to pass our screening process are purified and moved into the next phase of testing. Abeome’s scientists have also implemented a series of in vitro cell death assays to identify those that have unique cancer cell killing capability.
Following review of the relevant data, the mAbs are prioritized for analysis by tissue micro array (TMA) screening using immunohistochemistry (IHC). The TMAs are a critical step where we identify those mAbs which are binding to ovarian cancer human patient samples and not binding or lightly binding to a broad array of normal human tissue samples. Abeome has entered into an agreement with Fox Chase Cancer Center (FCCC) in Philadelphia to handle the TMA screening on this project. Fox Chase Cancer Center is one of the world’s leading gynecologic cancer research centers and is steeped in scientific talent with many years in the study of ovarian cancer. Abeome has delivered approximately 40 mAbs to FCCC for IHC.
Abeome’s OC project started with the immunization of approximately 50 mice with whole cells from four different OC cell lines. From these immunizations, the Company anticipates generating approximately 1,000 unique mAbs. (Click here to see current status of mAbs derived as of April 2009).
Researchers have found a number of stem cell mAbs which are cross reactive with the OC cell lines and we are continuing to screen ones of potential interest. We believe that by generating 1,000 OC mAbs in this experiment that we will have at least a handful of functional mAbs capable of becoming therapeutic products and another handful that are specific enough to OC cells (and which do not bind to normal ovarian tissue) to be developed into an OC diagnostic.
Future OC project milestones
Abeome is currently raising $1.5M is to help fund completion of a series of critical milestones associated the OC project. One of those milestones involves a crucial step to isolate the plasma membrane antigens (PMA’s) or surface proteins, to which the mAb’s are binding and then perform mass spectrometry to identify the specific PMA (the “targets”). As of the first half of 2009, the Company has a tentative identification of one of these targets and is prioritizing the target ID of any TMA-positive mAbs.
Positive mAbs on the TMA screen will also be involved in a mouse tumor xenograft study. This step will involve the transplant of human ovarian cancer cells into a genetic strain of immunocompromised mice. A set of control mice (untreated) will be anticipated to result in those tumors growing and advancing during the study. Another set of mice will be treated with Abeome’s OC mAbs. We will be looking to identify those mAbs that shrink and/or stop the growth of the tumors. from the first 26 mouse harvests. The current pool of 83 positive mAbs includes 31 that were discovered from a previous experiment using human embryonic stem cells as the immunogen.
