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Dr. Dan Claiborne’s Discoveries That Catalyze New Discoveries

March 18, 2024

Daniel Claiborne, Ph.D., was recruited to The Wistar Institute through the Caspar Wistar Fellowship program, which fast-tracks promising early-career investigators to full faculty membership. Now an assistant professor in Wistar’s major research centers — the Vaccine & Immunotherapy Center as well as the Ellen and Ronald Caplan Cancer Center — his team focuses on understanding the immune system to develop new, more effective immunotherapies against cancer and other deadly diseases.

How do you explain your job to a non-scientist?

My lab works on immunotherapies, which are ways to enhance the immune system to do a better job fighting diseases, cancer, or any threat. We work on cell therapy and engineer immune cells to express proteins that redirect the cell and impart specific functions so that they can be injected into someone and attack whatever disease is marked by the surface proteins we’re targeting.

Every scientist has their own approach to a question; our approach uses the research area of immunotherapy as a springboard to understand the fundamentals of our immune system. All the incredible tools in this field give us a unique opportunity to get into the real nitty-gritty of what’s happening on the minute level of cell biology and how immune cells interact within our biological ecosystem.

I have this tongue-in-cheek sign that says, “DON’T DO EFFICACY STUDIES.” It’s a reminder to ensure our interventions are effective, generate novel understandings of how immunity works, and do not focus exclusively on clearing viruses and diseases as the endpoint for the experiment. Experiments directly testing efficacy can be important for gaining valuable insight too, but I want to take the science further as our primary focus.

We know how to run a test with a T cell that can kill a virus in a dish or clear the tumors in a model. Those results show that we’re moving in the right direction. We also know that moving an effective treatment from lab model to a person comes with many complications and differing results. The “why doesn’t this work?” question is what keeps my lab and I purpose-driven.

You want to know where the stumbling blocks are so you can build better, more predictive models?

I’d go further: I only want to use models where our cell therapies don’t work (initially). Years ago, I heard this at a conference, and it’s stayed with me: “models are lies that help you see the truth.”

No model system is perfect, they are contrived by their very nature because we designed them, but if we build models that are sufficiently advanced and most importantly stringent enough then we can say, “The treatment we’re testing has a relatively high probability of being potent in a human patient because this model system is so rigorous.” We’re getting better at accounting for what our model systems don’t do and being honest about the limitations, while prioritizing models that give us results that are more likely to be translational, rather than those that give us “good results” all the time.

What is it that you don’t know and what are you looking for?

We know more about how to get a T cell to express a given protein than we do about the ins and outs of how the T cells in your blood “know” when something is wrong, or when T cells decide to ignore those signals. We don’t even fully know why T cells stop working if they’re over-exposed to antigens, for example, though many in the field have contributed valuable insights into this process in the past several years. The intricate information exchanges between immune cells aren’t known to scientists so much as they are theorized, and that realm of the unknown naturally draws me in.

What’s your hope for your research?

I want our findings to become treatments and cures. But more importantly, I want our deep dives into the immune system to generalize to other areas of disease, cancer, and immune research. That is the key for sustaining progress: discoveries that empower even more discoveries.

My lab works on T cell therapy for HIV. It would be great if, in the near future, we discovered the right formulation of CAR T cell proteins to cure HIV once and for all — but that’s probably not going to be the sole solution to the very complex problem, but worthy endeavor, of an HIV cure. More likely, T cells will be part of the solution that, one day, produces an HIV cure. When we understand that, I believe we’ll understand T cells’ role in a wide variety of applications, too. Step one to that level of understanding is learning the cells inside and out.