New Horizons Await Immunotherapy Beyond Oncology

“Muscle Tissue: Cardiac Muscle” by bccoer is licensed under CC0 1.0 

As the breakout therapy of the last 10 years, immuno oncology has established itself as the cutting edge of cancer therapeutics. By prompting the immune system to attack cancers in ever more sophisticated ways, immuno oncology has brought hope to countless patients for whom medical science had little to offer in the years prior.

Oncology isn’t the only domain in which immunotherapies can be life-changing for patients, however. The exploration into the full spectrum of immunotherapy’s possibilities outside of oncology is currently poised to become one of the biomedical sector’s most compelling trends. As of 2019, some research groups are starting to scratch the surface of using immunotherapies to address all kinds of pathologies ranging from heart disease to Alzheimer’s, and as research activity intensifies, more disease areas are sure to follow. While immunotherapy remains unproven within these other domains, researchers and companies seeking to get ahead will need to understand how the immunotherapy landscape is shifting and prepare accordingly.

Can Immunotherapy Disrupt Cardiology?

Heart diseases like cardiac fibrosis are treated with a myriad number of tried and tested interventions like implantable cardiac stents, which can provide life-saving relief for patients. But overall, mortality rates from heart disease remain high, and many of the available interventions are invasive surgeries that patients may not tolerate well. Thus, as unlikely as it may seem, novel immunotherapies may be able to revolutionize the treatment of cardiac pathologies and provide the option to treat patients who might not be otherwise eligible.

While clinical utilization of immunocardiotherapy remains distant for the moment, a research group at the University of Pennsylvania’s cancer center may be the first to utilize a cellular immunotherapy to treat a non-cancer pathology in vivo. According to their article published in Nature, the researchers developed a chimeric antigen receptor T-cell (CAR-T) therapeutic, which was capable of ablating the fibroid plaques responsible for heart failure in a mouse model. Importantly, fibroid plaques are excellent candidates for CAR-T immunotherapy because the cardiac fibroblasts responsible for the plaques express an antigen called fibroblast activation protein (FAP), which the surrounding cardiocytes do not. Though there remains a significant amount of research and development work before the new therapy can move to the clinic, the project is a convincing proof of concept for immunotherapy outside of oncology.

In the wake of the group’s paper in Nature, there will likely be a flurry of activity in big pharma laboratories re-evaluating cardiac pathologies with the aim of identifying potential immunotherapy targets. When immunotherapy targets are eventually found, developing the targets into new immunocardiotherapy drugs will be a significant research undertaking which will break open an entirely new field. But, much like with the original development of immuno oncology therapies, the practicalities of research will need to be addressed before any progress can be made.

New Challenges Await New Immunotherapy Research Domains

There are a handful of logistical and methodological challenges that will make it difficult to research hypothetical new applications of immunotherapy in domains other than oncology. While most of these challenges can be addressed, the first movers into the new research space will likely struggle the most.

Sourcing Skilled Researchers

Finding the right research personnel is likely to be a stumbling block for many companies. Interdisciplinary laboratory operations are already the norm, but the pairing of expertise from increasingly divergent fields will be necessary to take advantage of these new opportunities in immunotherapy. While there is an ample supply of experienced immuno oncology talent, staff with expertise in immunotherapeutics development as well as in an arbitrary pathology are almost certainly much rarer. This might make performing basic tasks like functional analysis or cell culture of disease-relevant cells to be more problematic than usual. More importantly, developing fruitful in vitro functional assays to measure therapeutic efficacy might require staff to use domain-specific techniques that they may not be skilled in.

Using Complex Experimental Models

Research into immunotherapy for non-oncology pathologies will likely utilize a higher frequency of in vivo models or complex in vitro models at an earlier stage than immunotherapy for oncology. While tumor cells readily grow in vitro and present their pathological impact on healthy cells in a handful of detectable ways, malfunctioning or diseased cells from arbitrary tissues may not be modelable without advanced techniques like 3D culturing. This means that researchers will need to move their experiments to animal models sooner to learn comparatively more basic facts about the performance of their therapy candidate. Furthermore, using more in vivo and complex in vitro models means that the costs of research in new domains of immunotherapy will be significantly higher than they were for immuno oncology.

Therapy Localization

New immunotherapies outside oncology will continue to struggle with the same drug localization obstacles as immuno oncology therapies as a result of using the same therapy modes, at least to start. This means that the highly specific nature of immunotherapies will be put to the test as a result of exposure to a plethora of non-target cells and tissues, much like in immunotherapy for cancers.

Cell therapies and antibody therapies will remain confined to circulation via the patient’s bloodstream, meaning that highly perfused organs like the heart and lungs will be easier for immunotherapeutic drug localization than the skin or brain. The result will be that new immunotherapies for these highly perfused tissues will reach the clinic much sooner than for other domains. Similarly, ensuring adequate therapeutic access to the areas affected by pathologies will be a significant challenge for new immunotherapies. While substantial headway in accessing the tumor microenvironment has been made in immuno oncology, it is unclear whether the same lessons apply to other dense tissue targeted by immunotherapies.

Building Momentum

Between the University of Pennsylvania group’s proof of concept for immunotherapy in cardiac disease and growing investment interest in the field of immunotherapy as a whole, the next few years will see an explosion of new research domains within immunotherapy. At the same time, maturing immunotherapies for oncology will continue to improve patient outcomes while treating a wider and wider range of cancers. In the biotech sector, numerous companies are developing new pathology-agnostic immunotherapy platforms, which could soon be ready for research use. While it’s impossible to predict which platforms and which new immunotherapy domains will be the most promising, it’s clear that oncology was only the first disease domain to be disrupted by immunotherapy, and that many more areas are soon to come.