Behind the Breakthroughs: Matthew Atherton

Behind the Breakthroughs is a Q&A series that shines a light on the people and ideas driving discoveries across Penn Vet. 

In this edition, we spoke with Assistant Professor of Immuno-Oncology, Matthew Atherton, BVSc, PhD, DECVIM. Dr. Atherton, a Diplomate of the European College of Veterinary Internal Medicine and member of the Penn Vet Cancer Center, is defining the prognostic and therapeutic role of T cells in blood cancers, utilizing a multi-species comparative approach.

With several novel targets for T cell-based immunotherapy identified and one ready to enter clinical trials, Atherton is convinced of their therapeutic potential in veterinary medicine and translational importance for human oncology.

What big problem is your research aiming to solve?

Immune therapies have revolutionized outcomes for numerous human cancer patients. As such therapies are generally not yet widely available for canine cancer patients, my lab is currently developing analogous cutting-edge immune therapies for veterinary use.

Our aim is twofold: firstly, we hope that we can deliver these promising new treatments to directly benefit the health of our canine cancer patients that we see every day at Ryan Hospital. Secondly, despite the universal promise of immune therapies, many people do not respond to these treatments. By using a comparative approach, we believe that what we will learn from our clinical veterinary trials will shed new light on how best to optimize immune therapies across species barriers, thus also benefiting people diagnosed with aggressive cancers.

What is the flagship project you are working on right now?

Since the inception of my lab in 2022, we have focused primarily on hematologic (blood) cancers in canine patients. Our studies have highlighted the potential to target these tumors using the patient’s own T cells as well as engineered canine T cells, known as CAR T cells, that safely redirect them to destroy cancer cells. Whilst we have several promising and novel CAR T candidates for different hematologic cancers, our most advanced platform targets histiocytic sarcoma, a devastating hematologic malignancy in dogs and humans alike.

This work, which is now primed to enter clinical veterinary trials, has been propelled forward by many clinicians, scientists, and students. However, a special mention must go to Dr. Lang Jian, an incredibly dedicated post-doctoral fellow in the Atherton Lab, who is responsible for translating our initial ideas into an actionable new treatment modality. Collectively, we are now all very excited to move into the clinical phase of this journey.

What is the one thing you wish more people understood about your field?

Unfortunately, many of our pets will be diagnosed with cancer in their lifetime. While laboratories that develop immunotherapies for the treatment of human cancer are comprised of a vast number of talented laboratory and clinical workers, the community developing veterinary immunotherapies, whilst also very talented, is considerably smaller.

Having witnessed some truly great responses in canine cancer patients treated with conventional therapies that can activate the patient’s own T cells, as well as newer, more targeted T cell therapies, I am truly convinced of their huge therapeutic potential in veterinary medicine. However, to come to fruition, our community requires additional resources that will allow us to unleash the full promise of cancer immunotherapy for the many veterinary patients that need more effective treatments.

What is the toughest challenge you face in advancing your work?

As the veterinary research community is small and funding sources are scarce, the development of crucial tools and reagents available to veterinary oncologists has lagged behind those developed for oncologists treating human patients, leading to a much smaller arsenal to fight analogous diseases. However, the many similarities between canine and human cancer patients have allowed oncologists treating human and veterinary patients to employ similar broad approaches between species governed by the unifying principles of surgery, radiation, and chemotherapy.

Unfortunately, as the margin of error in next generation immune therapies and personalized medicines is much smaller, subtle differences can dictate whether a new treatment succeeds or fails in the clinical arena. As such, while some canine and human tumors can be targeted by the same therapeutic, others cannot. The critical need to develop tailored tools and drugs for veterinary patients remains a major hurdle that can only be overcome by diversifying our intellectual and financial resources through the identification of alternative sources of support and finding more effective ways to collaborate and share our successful discoveries across our communities.

What is a passion or favorite ritual — outside your research and work — that helps to keep you balanced?

My wife and I have two very energetic young sons, a crazy young dog named Sophie, and a very gentle, middle-aged cat called Fergus, who manage to keep us both grounded and on our toes simultaneously. Beyond this, I am an avid supporter of Leeds United [soccer team].

Being a Leeds fan has certainly reinforced the fact that success is not always easy to come by—we’ve had our ups and downs. In our most successful era, we were captained by the fearless Scotsman Billy Bremner, who coined the term, “Side before self, every time.” Whilst Billy and his teammates played before my time, this statement really resonates with me. I consider myself to be incredibly fortunate to be surrounded by exceptionally supportive and talented people, both at home and at work. Although the challenges we face are significant, I believe that by approaching them as part of a team, we will have the greatest chance to succeed.