Building an inclusive, cross-cutting research immunology and immune engineering community
Once a week, Kelly McNagny sits in on meetings with medical doctors at St. Paul’s Hospital’s Centre for Heart and Lung Innovation (HLI), as they discuss their cases and their clinical research.
The experience changed how Dr. McNagny, a professor and Immunologist with UBC’s department of Medical Genetics, and the School of Biomedical Engineering, sees as the best way to do basic science research.
“I started realizing that if I had been sitting with these folks all along, I would have helped them tremendously with their basic approach to understanding disease, and they would have helped me design things that were more applicable for their clinics and patients’ needs,” says McNagny. “It takes these key interactions to shave years off of developing a new therapeutic approach to disease. Without them, it’s too easy to work and work, only to find what you’ve discovered isn’t what the patient needs or isn’t tailored in the right way for industry to manufacture.
“By being embedded with that group,” he adds, “I learned so much more about how to more rapidly address a real need, rather than my own scientific research backwater or research interest. I’m not being self-deprecating in any way…basic discoveries are essential. But it takes these interactions with the end users to put those discoveries to practical use. I think this is really important.”
The real need is vast: There are many diseases for which there is no treatment, or the powerful and sophisticated drug you are taking has side effects that create more problems, or more frequently, does not address the subtlety of your particular form of the disease.
Solutions lie in cross-disciplinary collaboration – Dr. Pauline Johnson and Dr. Kelly McNagny
“At the basic science level, the technique to generate monoclonal antibodies was made 40 years ago,” says Dr. Pauline Johnson, a professor with UBC’s department of Microbiology and Immunology. “And it has taken 30-40 years to develop monoclonal antibodies as immunotherapies to treat human disease. However, they are expensive to produce.” Examples of top-selling drugs in this class are Adalimumab, targeting Tumor Necrosis Factor, a substance in the body that causes inflammation, as well as Pembrolizumab and Nivolumab, which both target PD1, a protein found on immune cells.
Concerned by the translational lag between lab bench discovery and the production of drugs to treat patients, as well as the increasing evidence that immune and inflammatory cell behaviour and function contribute to all human disease and normal tissue repair, Drs. McNagny and Johnson have set out to shorten the way. On March 9, 2022, UBC’s Research and Innovation Office announced 40 research excellence clusters. Among the emerging teams was the new Immunotherapeutics Cluster, known as ImmunoT or ITC.
Co-led by McNagny and Johnson, ITC already has over 100 members, including graduate students, early career investigators, and clinicians. ITC’s goal is to develop a community focused on designing and developing the next generation of immunotherapeutics to promote health and prevent and treat disease. As a research-to-practice continuum, the cluster plans to link basic researchers with clinical disease specialists, industry partners and health-care economists and policy experts.
Why Now?
“I think the ‘why now‘ is because we have all of these new “omics’ technologies that allow you to address, in spectacular detail, how diseases come about,” reflects McNagny. “We’re starting to realize that if you use those cutting-edge tools to specifically address individual diseases, you can quickly pick out the specific immune component that’s gone wrong, and drives the disease. That knowledge, in turn, gives you the opportunity to rapidly fix the problem with a new custom therapeutic tool to target those cells or pathways and address individual diseases, rather than using more blunt instruments with unwanted side effects.”
Akin to precision medicine, with its focus on genetic or molecular profiling, but with a broader tool kit, and an explicit immunological focus, immunotherapeutics has only recently gained attention beyond its use in cancer and infectious disease.
“Virtually any disease you can name has an immunological component,” says Dr. Johnson. “The trick is to find out how that component influences disease outcome and then manipulate it in a way that helps the patient.”
UBC is home to a number of leading basic immunologists and basic biomedical researchers who have the background and potential to drive immunotherapy forward. Drawing on this expertise, the ITC will initially focus on five areas:
• Novel antibodies and antibody-targeted drugs
• Novel cell-based therapies
• Cytokines and immune-agents
• Lipid nanoparticle and mRNA-based vaccines and therapeutics
• Microbiome alterations
In addition to the right time for such a network, McNagny points to British Columbia as being the right place, as well. “You can tell from the breadth of biotech industry we have in Vancouver,” he says. “we’ve got AbCellera, which is a multi-billion-dollar company, we’ve got StemCell Technologies Inc (Canada’s largest biotech) and Amgen’s antibody-based R&D lab and a slew of new smaller start-ups. The city is becoming an immunology hotbed for corporate interests. I think the time is right to link those people, with basic researchers, clinicians and patient groups in way that would be transformative for BC.”
Alveolar macrophage full of lipid droplets | Jeff Dong, Johnson lab
Both Johnson and McNagny agree that COVID-19 and the advent of mRNA vaccines delivered via lipid nanoparticles have opened the door to less expensive drug delivery than current methods. Currently many immune therapeutics are given in doctors’ offices and clinics via intravenous infusions.
“Immunotherapeutic approaches to treating cancer are really hot these days,” observes McNagny, “but frequently those approaches are not more widely used because the cost is so high, and the infrastructure is too complex for the average clinic. You might see that in a metropolitan cancer clinic, but certainly not in a rural medicine clinic, so, if you really want to build an immunotherapeutic that’s going to reach those people, you’re going to have to think in a different way.
“Likewise, he adds, “if you want to see those same types of immunotherapies applied to more common chronic disease, you’ll need to design more accessible approaches.”
Lipid nanoparticle portend all kinds of exciting possibilities. “Talk about something that reaches every community and is cost-effective and economically viable,” says McNagny. “My friends in the vaccine field are thrilled about this, because they’re saying this is going to be a new approach to treating parasitic diseases, and other things that have been really tough to treat before. It’s also a beautiful example of a huge need that was spurred by a big crisis, and some great scientists with out-of-the-box ideas came in and solved it. “
Early priorities
With UBC seed funding for the first year, ITC will move to expand membership – all interested parties are welcome – and lay the groundwork for operationalizing its commitments to equity, diversity and inclusion and a translational focus. Training, and trainees are seen as a top priority. The ITC proposal outlines a cross-disciplinary, inclusive trainee community with direct ties to experts in immunology and immunoengineering. A competition will be held for a partial fellowship to obtain preliminary data to support collaborative projects. Workshops and trainee-led meetings will expose trainees to the full range of network membership and perspectives.
Macrophage engulfed by Staphylococcus aureus | Jeff Dong
“When trainees hear these presentations, it’ll change the way they do their business,” says McNagny. “We want those ideas springing out of trainees.”
In addition to invaluable experiential learning and exposure, good job prospects await ITC trainees. “When I talk to folks in industry, they are desperate for bright young students to come through with an immunology background,” says McNagny.
Interested in participating as a trainee, researcher, clinician or industry partner? The network has set up an online membership application.
In building the network, “we really want to be all-inclusive,” states McNagny. “If you’re going to make big breakthroughs these days, I think everyone understands it takes a village. We want to have people with different views, different technologies, and different ideas, sharing their ideas openly, so we can work as a team, rather than as an individual or a lone gun in our silos. I don’t want to see siloed research ever again. It’s when you put really smart kids with different toys and ideas together in the same sandbox that magic starts to happen. That’s our goal.”
“Immunology and the distinction of self and non-self is at the heart of keeping us safe from infection and cancer,” concludes LSI Director Dr. Josef Penninger, a member of the ITC. “Much has been learned and based on this, amazing breakthroughs have been made. Just think about the COVID-19 vaccines or the new world of cancer immunotherapies. The new immunotherapeutic network will enhance the visibility of immunology at UBC and has the promise to develop radical new therapeutic solutions for many diseases.”
Read: Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes a pre-print publication arising from Dr. McNagny’s collaboration with clinicians at St. Paul’s Hospital’s Centre for Heart and Lung Innovation (HLI).