In the next five to ten years, what two key things could improve T cell therapy?
The number one thing is the T cell therapy needs to have some success in solid tumors—expanding beyond hematological diseases. The longer term is beyond solid tumors, and T cell therapy has the potential to treat viral infections, such as Epstein-Barr virus and HIV.
Secondly, we need to find a way to make it safer. Then, we can expand to first-line treatments of diseases and move to outpatient settings. We’re probably still years away from that, but many companies—including us—are developing techniques toward this goal.
There are three different strategies to improving safety. One is managing safety from a clinical perspective: looking at biomarkers to know the early signs of a problem and then managing the patient quickly. The second strategy is developing kill switches, on-and-off technology, to shut down T cells when needed. The third approach, our approach, is to design a T cell therapy that doesn’t over activate T cells. That way, you don’t get the terrible toxicities in the first place.
Conceptually, we can change how we treat cancer. In the past, it was all about prolonging survival—a few more months or years. Now, we want cures.
What are the complications to attaining those improvements?
So far, a majority of the success of immunotherapy is against general targets that shield cancer cells from the immune system. To achieve success in solid tumors, we need to find tumor-specific antigen targets—what we call TSAs. I think we are reaching a consensus that the majority of those tumor-specific targets reside inside the cancer cells (see ‘The Tell-tale Targets Hidden Inside Solid Tumors’). So, intracellular targets are the gold mine, and we need to go after them.
Our E-ALPHA platform contains more than 100 billion clones with unique human antibody sequences. It lets us quickly identify antibodies that target fragments of tumor-specific antigens on the major histocompatibility complex, which is involved in turning on acquired immunity. We use this to develop novel T cell therapies directed toward many types of cancers. Further, our platform is designed to allow for the targeting of both extracellular and intracellular targets expressed in both hematological and solid tumors. You have to somehow learn about what nature does, and then make use of that to engineer a treatment. That’s what we do.
What has been the biggest inspiration or change in the way of thinking about T cell therapy?
The nature of science is thinking in new ways. When we started our approach eight or nine years ago, people didn’t think we’d be able to attack molecules that come from inside cells. So, you have to think boldly. But it didn’t come from just us. Starting 30 or 40 years ago, advances in molecular biology—such as the creation of monoclonal antibodies—laid the foundation for Eureka Therapeutics.
To learn more about the development of T cells for therapeutic use, visit the report from Scientific American Custom Media, Frontiers in T Cell Therapy.