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Clinician Spotlight: Dr. Alexandre Reuben

*April 2024*

This month, we are honored to feature Dr Alexandre Reuben, PhD, assistant professor in the Department of Thoracic/Head & Neck Medical Oncology at MD Anderson Cancer Center. Dr. Reuben’s research aims to understand how to boost the body’s T-cell response against lung cancer, uncovering resistance mechanisms within the tumor microenvironment. 
Dr. Reuben received the 2023 EGFR Resisters/LUNGevity Research Award for his work in Using T cells to Tackle Drug Resistance in EGFRm Lung Cancer. The research will focus on T cell engineering to develop more effective therapies for people with EGFRm lung cancer. Read about this study here.

What motivated you to get involved with lung cancer research? How did you do it?

My primary fascination has always been with the immune system and how it protects us from diseases on a daily basis. Conversely, I’m terrified by cancer and amazed at how it is constantly evolving, becoming stronger, and seeking to escape the immune system. This is what drew me to want to study the interface between the immune system and cancer. I obtained my Ph.D. at the University of Montreal in Canada studying how the immune system recognizes viral infections and skin cancer/melanoma. I then moved down to MD Anderson in Texas for a postdoctoral fellowship with the intent to return to Canada to build my lab, but I ended up never looking back. MD Anderson’s resources and proximity to patients are something which can be experienced in a very limited number of centers across the world, and this was exactly what I was looking for to make sure our research had the maximal impact on patient lives. I established my lab at MD Anderson in 2018 and we have been developing immunotherapies using a patient’s own immune cells to treat lung cancer since then.

What research have you done that would have the most impact on our members with the EGFR mutation?
I’m most passionate about immunotherapy, leveraging one’s own immune cells. Among these immune cells, T cells are involved in directly recognizing and killing cancer cells, but they can be present in low numbers making them ineffective at destroying tumors. Accordingly, a key area of research of our lab is our T cell engineering work. Through these studies, we have generated a series of receptors which, when genetically engineered onto immune cells, give them the ability to both see and destroy tumors harboring EGFR mutations.

What new projects are you working on?
As a result of support from the EGFR Resisters and LUNGevity, we are now in the process of investigating the impact our T cell engineering studies could have on drug-tolerant persister cells and drug resistant cells. This work would not have been possible without the support of the EGFR Resisters and LUNGevity, and we hope this will prevent the development of resistance to osimertinib in patients with EGFR mutations.

What was treating lung cancer/lung cancer research like when you first started to practice, and when was that?
When I started doing research in the 2000s, the role of the immune system in protecting us from cancer and its therapeutic potential were heavily under-appreciated and largely dismissed. Now, it’s impossible to go to a cancer conference without hearing about immuno-oncology (immunology of cancer). The advances made over the last 10-15 years have definitively established the role of the immune system in protecting us from cancer and launched immunotherapy into the mainstream. This has made it considerably easier for us all to explore these types of questions in our research labs.

What do you think lung cancer treatment will look like five years from now?
As a scientist who does not treat patients, I can only speculate about treatment-related issues, but in my opinion, personalizing treatments is the way to go. By better understanding each patient’s cancer and the strengths and weaknesses of their immune system, we can develop tailored therapies that would hopefully lead to improved benefits for patients. Concretely, this would mean having additional information pertaining to a patient’s tumor genomics (what genes and mutations are present) and immune system (which immune cells are present in the patient’s blood and tumor and how they are behaving), among other things.

What treatments/research of interest do you consider will make a significant impact in the not-too-distant future?
Without a doubt, cell therapies. We now know antibody therapies such as checkpoint inhibitors (nivolumab, pembrolizumab, durvalumab, etc.) can result in miraculous responses. However, using immune cells is what we’re most passionate about. There are significant challenges and costs associated with this type of therapy however the potential is endless because this is a “living” therapy that can continue to persist, evolve, and grow with the patient