NanoCell Therapeutics establishes home base in Utrecht Science Park

Quality infrastructure and interdisciplinary cooperation

Start-up company NanoCell Therapeutics, which develops a nanomedicine to cure cancer and other diseases, establishes its home base on the Utrecht Science Park. The company was drawn by the high quality infrastructure at Utrecht University, as well as the prospect of interdisciplinary collaborations with both the university and UMC Utrecht.

Prof. dr. Enrico Mastrobattista, Maurits Geerlings en prof. dr. Raymond Schiffelers
Prof. Enrico Mastrobattista (Utrecht University), Maurits Geerlings (NanoCell Therapeutics) en prof. Raymond Schiffelers (UMC Utrecht)

Since 2017, oncology has welcomed a new type of cancer treatment: CAR-T immunotherapy. “In CAR-T cell therapy, a specific type of immune cells called T cells are taken from the patient’s body. The cells are then genetically modified in the lab. They are given a receptor that allows them to recognize and kill tumor cells very specifically without affecting the surrounding healthy cells”, says Enrico Mastrobattista, Professor of Pharmaceutical Biotechnology and Delivery at Utrecht University.

One of the first approved applications of CAR-T cell therapy is to treat acute lymphoblastic leukemia (ALL), a form of blood cancer in which white blood cells proliferate rampantly but fail to grow into the correct form. Each year ALL is diagnosed in more than 170 patients in the Netherlands. ALL patients usually receive chemotherapy, but for many of them only CAR-T offers a permanent cure.

Solution for highs costs and drawbacks

CAR-T is a revolutionary and successful treatment. In the Netherlands, the treatment is mainly performed at the Utrecht-based Prinses Máxima Centre. The treatment does have serious drawbacks, and pharmaceutical entrepreneur Maurits Geerlings of NanoCell Therapeutics has found a possible solution to those problems. In the 1990s, Geerlings studied Pharmaceutics in Utrecht. Over the past 20 years he has set up several biotech companies in the United States, including genetic engineering to treat cancer.

Maurits Geerlings of NanoCell Therapeutics found a possible solution for CAR-T's drawbacks

Geerlings talks about the shortcomings of CAR-T in its current form, with the extremely high price perhaps being the most important. “The production costs of such an autologous CAR-T treatment, whereby the body’s own cells are isolated and modified separately for each patient, are about 100,000 euros per patient alone. On top of this are the development costs of the therapy and the individual medical costs. When combined, this can push the cost per patient up to a million euros. This makes it socially unaffordable to treat large numbers of patients. In addition, there are unpleasant side effects that in some cases land CAR-T patients in the ICU.”

Leaving the hospital, the day after treatment

But even without serious side effects, the burden on the patients is substantial, says Enrico Mastrobattista. “Between harvesting and insertion of the modified T-cells, the patient has to stay in the hospital. During that period, the patient receives chemotherapy. In addition, keeping T cells outside the body to modify and expand them reduces their therapeutic strength.”

In vivo cell engineering could resolve obstacles that gene therapies currently face

Geerlings and his team therefore work on a solution to the obstacles that CAR-T, as well as other gene therapies, currently face. They are developing nanoparticles to specifically target T cells inside the patient’s body. The particle can genetically modify T cells inside the body after administration. This way, Nanocell Therapeutics brings about the concept of in vivo cell engineering – that is, in the patient’s body. Mastrobattista outlines the enormous effect this will have on the treatment process: “A patient would then already be able to go home the day after treatment.”

Utrecht, rather than Berlin, Leuven or Milan

The equipment needed for the research of Nanocell Therapeutics turned out to be unaffordable for a start-up company. That’s why Geerlings started a search throughout the US and Europe for a location that offered the optimal combination of the right equipment and the opportunity to collaborate. “I looked in Berlin, Leuven and Milan, among other places. Through the Utrecht Science Park, I came into contact with the Pharmaceutical Sciences department of Utrecht University and the UMCU. The atmosphere here is very interdisciplinary. Also Utrecht Inc. facilitates us.”

For us it's a great opportunity to demonstrate the relevance of our research to society

In the collaboration with Pharmaceutical Sciences, Geerlings sees opportunities to improve the specificity of the nanoparticles. Enrico Mastrobattista looks forward to this. “We have a lot of knowledge in this field and can provide the infrastructure. It is for us a great opportunity to be able to demonstrate the relevance of our research to society in this way.”

Also for poorer countries and other diseases

In any case, Geerlings has ambitious plans. He hopes to develop gene therapy for cancer and other life-threatening diseases. “Ultimately, we want therapy to be accessible, scalable and affordable – not just in the West, but also in poorer parts of the world.”

The therapy should be accessible, scalable and affordable, also in poorer parts of the world

When that goal is achieved, the partners will jointly focus on developing these targeted nanoparticles to fight other diseases. Geerlings: “It doesn't necessarily have to be T-cells. It can also work for various other types of cells, such as B-cells and liver cells. It is then important to make the right coating around the active nanoparticle. We have plans for the future to also focus on autoimmune infectious diseases such as rheumatoid arthritis, or inflammation in the joints. Examples of which are atherosclerosis and rare genetic metabolic diseases, to name just a few applications.”

Introducing RNA and DNA into cells

From the University of Twente and its spin-off company 20Med Therapeutics, a nanoparticle technology has been developed that allows RNA and DNA to be introduced into cells. To be able to integrate the DNA with the genome of the T-cell, NanoCell Therapeutics uses a so-called transposon technology, an alternative technique for transfecting genetic material without the need to draw on viruses (lenti-, retro- or adenovirus). In addition, the company uses advanced minicircle DNA technology (mcDNA) for the production of the therapeutic DNA. mcDNA is much smaller than conventional DNA, and therefore makes transfection much more efficient. In coming years, Nanocell Therapeutics aims to further develop the basic technology, paving the way for therapeutic products, first preclinically and then followed by clinical phases.