Researchers at the University of Louisville have been testing a protein-based molecule they originally developed to boost the power of T cells in treating cancer. But in the course of testing the protein in mice, they made a surprising discovery: The drug, dubbed SA-4-1BBL, protected normal mice from developing cancer in the first place.
The team developed SA-4-1BBL to be used in conjunction with adaptive T cells that would be trained to target tumors for destruction. But when they gave the drug by itself to healthy mice, and then exposed the mice to cervical and lung cancer cells, the animals were largely protected against tumor development for more than eight weeks. The researchers reported their findings in the journal Cancer Research.
"The novelty we are reporting is the ability of this molecule to generate an immune response that patrols the body for the presence of rare tumor cells and to eliminate cancer before it takes hold in the body," said Haval Shirwan, Ph.D., a professor at the University of Louisville Institute for Cellular Therapeutics, in a statement.
Shirwan and a fellow faculty member, Esma Yolcu, Ph.D., have started a company, FasCure Therapeutics, to further investigate the potential of SA-4-1BBL in immuno-oncology.
In the study, Shirwan and his colleagues demonstrated that their novel protein activates CD4+ T cells and NK, or “natural killer” cells in the immune system. This creates an immune surveillance system, they believe, which travels around the body, eliminating cancer cells before they can form tumors.
To confirm their hunch, they eliminated CD4+ and NK cells in a group of mice and then tested SA-4-1BBL. Those animals were not protected from tumors.
T-cell cancer treatments have revolutionized the oncology field over the past two years, with the approval of the personalized CAR-T therapies for blood cancer, Novartis’ Kymriah and Gilead’s Yescarta. But they require removing T cells from individual patients and then training them to recognize and attack their cancers. The cumbersome nature of that—not to mention the cost—has some companies searching for off-the-shelf alternatives, including Fate Therapeutics. One of its experimental cell therapies, FT500, is an NK cell made from induced pluripotent stem cells.
The University of Louisville team is encouraged by the fact that their protein molecule seems to stimulate the immune system without the need to also inject T cells. What’s more, the drug didn’t cause significant side effects in mice, the researchers reported, and it’s unlikely to cause an immune overreaction because it only activates disease-fighting cells that exist naturally in the body.
FasCure collaborated on the research and has an option to license SA-4-1BBL from the university. Shirwan hopes to further test the potential of the drug for cancer prevention, though he concedes choosing the right patient population for clinical trials will be challenging. One possibility is to test it in people who are genetically predisposed to certain cancers, he said, or who have precancerous lesions.