With the discovery of an unexpected protein on the surface of cancer cells, UVA Health researchers are on the cusp of finding new approaches to treat difficult cancers.
This new research, currently led by Craig Slingluff Jr, MD, focuses on the function of a protein, SAS1B, that may prove an important marker for immunotherapy treatment for diseases ranging from pancreatic to ovarian cancer.
The researchers published their findings in the Journal for ImmunoTherapy of Cancer.
Translating Contraceptive Research to Cancer
Slingluff began his research after a colleague, John Herr, PhD, found and identified the SAS1B protein as a potential target for contraceptive vaccines. This protein normally functions in sperm-oocyte interaction during conception. But Herr’s team found that it was expressed on some cancer cells, and they developed antibodies that may be used to target them on the cancers.
Herr came to Slingluff, a surgical oncologist and translational immunologist at UVA Health, to collaborate on how this new information could be used to treat patients through novel approaches like cancer vaccines or CAR T-cell therapy. The Cancer Research Institute funded Herr and Slingluff as a team to continue these studies. Sadly, Herr passed away before the research was completed. But Herr's team, along with Slingluff, have continued this promising research.
As the research team dug deeper, they found the SAS1B protein is expressed in some normal tissues, including islet cells in the pancreas. They were interested in whether cancers and normal tissues differed in how or where they express SAS1B. Interestingly, they found that this protein is expressed inside normal cells, but on the surface only of cancer tumor cells.
Addressing Urgent Need for Better Cancer Treatments
This revelation meant the possibility of new treatment options. For example, the team hypothesized that using an antibody that only binds to surface proteins should be able to treat cancer cells without hurting normal cells. That directed the team’s focus toward antibody therapy, including antibody-drug conjugates with toxins.
Similar drugs have been approved by the Food and Drug Administration for the treatment of other targets, but new drugs could focus on treatment for new targets like pancreatic cancer and ovarian cancer — diseases for which immunotherapy has not been effective so far. Their data also show promise for other cancers for which immunotherapy can be effective, such as breast cancer, renal cell cancer, and melanoma.
“Cancer still kills a lot of people,” says Slingluff, the Joseph Helms Farrow professor of surgery. “Although there have been great advances in treating various cancers, there is still an urgent need for better treatments for most cancers.”
Slingluff’s team conducted research in vitro with human samples. Future research will focus on testing whether the antibody-drug conjugates the research team identified can work in vivo on human tumors in mouse models.
Exploring SAS1B as Therapeutic Cancer Target
Slingluff has collaborated with leading researchers across other disciplines as these studies, and potential treatment options, have progressed. In particular, Slingluff is working closely with colleagues in radiology to find better ways to test for and identify these proteins on the surfaces of cells.
“There is a strong collaborative spirit at UVA Health,” says Slingluff. “It is easy to work together here because everyone wants to make progress together. Dr. Herr’s staff remained very involved in the work and cared enough about it to keep it going and collaborate on our research.”
UVA Health also brings expertise in adoptive cell therapies, including CAR T-cell therapy, which can serve as potential targets for the antibodies identified in this study. As an NCI-designated Comprehensive Cancer Center, UVA Health fosters translational research to quickly get novel therapies from the lab to patients.
“There is reason to be hopeful for new treatments for cancers that aren’t responding to current treatments,” says Slingluff. He and the research team conclude, "These findings support further exploration of SAS1B as a potential therapeutic cancer target in multiple human cancers, either with antibody-drug conjugates or as a chimeric antigen receptor-T (CAR-T) cell target.”
