Holy Grail: Dr Ian Parish on repurposing drugs to expand immunotherapy-responsive killer T cells

Can you sum up the aim of your project in 10 words?

To boost the efficacy of cancer immunotherapy using approved drugs.

What aspect of this research excites you the most?

The most exciting part of this research is that, because we’re working on repurposing drugs that are already approved, any findings that we make could be rapidly translated to the clinic.

What have you previously discovered in this area?

Our previous work in this area has focused on deciphering the molecular circuitry that switches immune cells off and stops them from functioning in a range of contexts, including cancer. We’ve identified a number of important molecular switches that regulate this process.

What led you to look at thalidomide derivatives over other existing or new drugs?

Our work on thalidomide derivatives is pretty serendipitous. We were researching the basic biology of a process that prevents T cells from attacking tumours. We identified a novel pathway that controls this process, and this pathway just happens to be blocked by thalidomide derivatives.

What’s the potential impact of your research?

Our research could identify a way to pre-condition cancer patients so that more patients respond to checkpoint blockade immunotherapy. One of the major impediments to the success of checkpoint blockade is the absence of therapy-responsive T cells in the subset of patients that are refractory to therapy. We’ve identified a pharmacological approach that could restore and boost this cell population. This could both improve outcomes in responsive patients and increase the proportion of people that respond to therapy.

How long before your work might impact patient care?

If all goes well and our predictions are borne out in our preclinical work, we could, in theory, start planning for a clinical trial within the next few years. The huge advantage we have is that we’re working with drugs that are already approved for clinical use.

What’s your Holy Grail — the one thing you’d like to achieve in your research career?

My Holy Grail would be to identify a completely new paradigm in my field that ultimately transforms clinical practice. For example, the initial work that led to checkpoint blockade immunotherapy was curiosity-driven research aimed at understanding how immune cells are wired. They didn’t set out to transform cancer therapy. I’m a passionate believer that the biggest changes in how we treat disease are always initiated by a paradigm shift in fundamental biology. This is something that I’d love to achieve.

What is your biggest research hurdle?

My biggest research hurdle is the same hurdle that everyone in research currently faces: tracking down enough funding to continue (and ideally expand) my research program. Much like my peers, I spend a lot of my time writing grants. To sustain a research program currently, you need to pursue absolutely every possible funding avenue available.

Who has inspired you in your work or life?

I’m lucky to have had a number of inspirational mentors across my research career who’ve taught me a lot. My father is a researcher with a passion and excitement for what he does, and that enthusiasm is what first led me to research. I’ve since had a number of amazing mentors who’ve taught me many things: how to conduct rigorous research, how to pursue big ideas and how to manage and mentor a team.

What has helped your spirits most during COVID-19?

As much as juggling remote learning with work has been really tough, my family has helped me get through the last 18 months. I’ve really enjoyed the extra time spent with my kids, it has been an unexpected positive in the current situation.

Dr Parish spoke to Natasha Doyle.


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