Our third interview for “SPInform” is with Filipe Pereira, a group leader at CNC Coimbra (and also at the University of Lund, Sweden), who has just been awarded a Pfizer Award for Basic Research 2024 for his work on reprogramming tumor cells into antigen-presenting dendritic cells. His latest paper on the topic recently came out in Science: https://www.science.org/doi/10.1126/science.adn9083. Below you can read about this work in his own words, and find out what were Filipe’s key steps in Immunology, and what are his goals for the future.
Short biography
Filipe Pereira is a Full Professor in Molecular Medicine at Lund University, Sweden. His research group is based at Lund University (Sweden) and at the Center of Neuroscience and Cell Biology, University of Coimbra (CNC-UC, Portugal). He is recognized for his work at the interface of cellular reprogramming and immunology and for fostering the development of reprogramming-based immunotherapies. He pioneered the induction of dendritic cells from fibroblasts and cancer cells. He co-founded Asgard Therapeutics, which received investment from leading European VCs to translate in vivo dendritic cell reprogramming to benefit cancer patients. For his scientific accomplishments and innovation efforts, he received several awards, including grants from the European Research Council, the Novo Nordisk Distinguished Innovator, and the Wallenberg foundation project grants. He was also awarded the prestigious Swedish Fernström Prize, the entrepreneurship award from Mount Sinai-KiiLN and a medal of merit from his hometown in Portugal. Recently, he and his team were awarded with the Pfizer Award for Basic Research.
1. When and how did you become interested in Immunology?
I was introduced to Immunology by professor Fernando Arosa and Professor Maria de Sousa at the University of Porto early in my research career. I then started the GABBA PhD program and remember reading the “histone code” (Jenuwein and Allis, 2001), that set in motion my interest in epigenetics. In addition, one of the reasons I chose to pursue a biology degree at University of Porto was the cloning of Dolly the sheep in 1997. It fascinated me how a single cell could originate a whole organism. So, I decided to study epigenetics and cellular reprogramming during my PhD. Yet, I never put Immunology aside as I was reprogramming B cells to pluripotency using cell fusion. During my postdoctoral studies, I established reprogramming towards the hemogenic endothelium, which generates hematopoietic stem cells, the mothers of all immune cells. Interestingly, that initial year where I explored immunological concepts was really important to identify knowledge gaps when starting my independent research group.
2. What do you perceive as key decisions during your training and career?
Moving and getting exposure to different scientific environments was critical for my scientific growth. During my PhD in London, I learned from my mentor Amanda Fisher how to ask good questions and design innovative experimental systems to answer them. In NYC, as a postdoctoral researcher at Mount Sinai School of Medicine, I learned a lot about project execution and how to translate my science with my visionary mentor Ihor Lemischka. The motto “we will make it happen and learn along the way” molded the way I now lead my group. The decisions to move back to Portugal in 2015 and move to Sweden in 2017 were also key: in Portugal I started my own group and had the scientific freedom and time to think outside the box; moving to Sweden supported my research projects financially and my group members with an extended network.
3. How do you manage two labs so far apart, one in Coimbra and the other in Lund? How different are they?
Zoom is a fantastic tool! The lab in Portugal is crucial for young researchers to start their careers and the lab in Sweden currently has more senior researchers. Both labs complement each other in terms of expertise and career stages; they are far apart in distance, but not in scientific interaction. We have shared lab meetings and shared cloud-based organization. My team also has a component of research support, composed by a Project Manager and Science Writer that work remotely. So, the way research groups work today really go beyond frontiers. It is more about finding the right people and the right talent. So, cooperation is essential in my group, particularly in the ambitious consortium-based projects, that count with contributions from group members from Portugal and Sweden but also from people from many other countries that bring unique expertise.
4. Can you explain your main findings of the research distinguished with the Pfizer Award and its follow-up that has been recently published in Science?
The research distinguished with the Pfizer Award and published in 2023 in Science Immunology was based on testing the hypothesis that we could turn tumor cells into antigen-presenting dendritic cells. We successfully reprogrammed a wide range of mouse and human cancer cell lines and established proof-of-principle that this process elicited robust antitumor immunity. Then, we wanted to facilitate translation of our approach, surpassing challenges associated with regulatory approval of isolating tumor cells, reprogramming in vitro, and reintroduction in the patient. Hence, we developed an off-the-shelf therapy and reprogrammed cancer cells into dendritic cells in vivo with an adenoviral vector that delivers the reprogramming factors to tumors – those findings were recently published in Science (Ascic et al., 2024; https://www.science.org/doi/10.1126/science.adn9083). In this study, we provided preclinical proof-of-concept of an in vivo immunotherapy modality that orchestrates long-lasting antitumor immunity.
5. What are the research questions that excite you the most for the future?
We will test our reprogramming strategy in clinical trials in 2027 and it will be exciting to see whether anti-tumor immunity will be launched in humans. This will be the first in vivo reprogramming approach in humans. Our findings opened additional exciting paths: we are testing the hypothesis of identifying immunogenic tumor-specific antigens with reprogramming, which may lead to improve adoptive T cell therapies and cancer vaccines. The possibility of reprogramming other types of immune cells that activate different immune responses (eliciting immune tolerance, for example) would also be very valuable for fighting autoimmune diseases. Overall, I am keen on understanding better the reprogramming process, identifying mechanisms that can help us change cell identity efficiently and at high fidelity.
6. What do you consider as main challenges for researchers working in Portugal when compared to Sweden?
The biggest challenge for researchers in Portugal is the lack of funding and a low critical mass in certain fields. We have resources, technologies, and excellent researchers in Portugal, but stimuli and commitment with researchers is limited. There is rather a uniform division of resources which sometimes spread thin the research efforts of our nation. We need to increase the flow of people and knowledge and develop a stronger research support system for the most promising researchers, while at the same time promoting the existing horizontality, scientific freedom, and excellence in training.
