Willem Mulder is closing the gap between application of nano-immunotherapy on mice and on humans

August 27, 2019

His study demonstrates that the therapy is effective across species, bringing the day it can be used to cure humans much closer.

This image is a 3D volume-rendering of the MRI sequence used for assessment of vessel wall permeability (3D dynamic contrast-enhanced MRI) of one of the pigs in the study, before and after treatment with the nanoimmunotherapy.

Results published last week in the journal Science Translational Medicine represent a big leap towards using nanotechnology as next generation immunotherapy to fight cardiovascular disease. An international team led by professor Willem Mulder from the Eindhoven University of Technology (TU/e) and Icahn School of Medicine at Mount Sinai completed a five-year research demonstrating that nano-immunotherapy is effective in cardiovascular disease across different species, bringing this technology close to clinical application.

The potential of nano-immunotherapy
Nano-immunotherapy is a new application of nanotechnology. It has the potential to address several serious human health issues, including cancer, cardiovascular disease, and autoimmune disorders. It could also offer an alternative to a lifelong course of immunosuppressant drugs for organ transplant recipients. Nanomedicine, the medical use materials or devices measured in billionth of a meter, has been the subject of decades of research, but largely as a mechanism to deliver toxic drugs to tumors. The burgeoning field of nano-immunotherapy looks at how nanotechnology can empower the body’s immune system to combat disease or ‘educate’ it not to attack transplants.

The breakthrough
After a five-year study, Mulder and his team now show promising results of nano-immunotherapy in rabbit and pig models of cardiovascular disease. Previously, they demonstrated this approach to be successful in mice. To facilitate clinical translation, however, studies in large animal models are highly valuable. This presents a challenge as not only are the subjects much heavier, which requires scaling up nano-immunotherapy production, they also have longer lifespans and take longer to reproduce and therefore are much costlier. Mulder’s team solved the problem by integrating multimodality clinical imaging to longitudinally monitor the therapy’s effects, non-invasively. Their research demonstrated that the therapy is effective across species, bringing much closer the day it can be used to cure human beings of serious ailments like cardiovascular disease, as shown in this study, but also auto-immune disorders and cancer.

The team
Mulder led an international team of renowned investigators, consisting of people with highly diverse backgrounds, including biomedical engineers, imaging scientists, immunologists, physicians and clinicians from prestigious institutions in the US (Icahn School of Medicine at Mount Sinai, New York University, Massachusetts General Hospital/Harvard, Memorial Sloan Kettering Cancer Center), the Netherlands (TU/e, Radboudumc, Amsterdam UMC) and Denmark (University of Copenhagen).

Willem Mulder is a TU/e grad and established a Precision Medicine group within TU/e’s Department of Biomedical Engineering in September 2018. In 2006, he founded the Nanomedicine Laboratory at Icahn School of Medicine at Mount Sinai School in New York, where he is a professor in the Department of Radiology. Today’s research adds to the team’s significant body of findings about the use and efficacy of nano-immunotherapy.

“This paper showcases how we matured as a research group and how we integrated several biomedical engineering disciplines to get the application of nanomedicine as an immunotherapy close to clinical translation”, prof. Willem Mulder said. “It has been ten years since we started conceptualizing the development of a strategy towards evaluating nano-immunotherapy in large cardiovascular disease animal models. For mouse models, several well-validated essays are available to evaluate disease state, but for our work in large animal models we had to develop an evaluation strategy that relied on the exploitation of noninvasive imaging. Using three-dimensional integrated PET/MRI and PET/CT on clinical scanners allowed us to study important aspects of cardiovascular disease with unprecedented accuracy.”

Dr. Zahi Fayad, director of Mount Sinai’s Translational and Molecular Imaging Institute, concludes: “NHLBI’s Program of Excellence in Nanotechnology was the genesis of our world-class Nanomedicine Program that continues to be highly productive and innovative, yielding many opportunities for precision imaging and treatment of patients. With Mount Sinai’s support, we are hopeful to start clinical trials within the next five years.”

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