Successful researchers attract huge investment for Trojan attack on cancer cells

Researchers from Finsen Lab, Rigshospitalet and Biotech Research & Innovation Centre (BRIC) have developed a form of chemotherapy that can kill cancer cells from within using a unique Trojan Horse strategy. The technology is so promising that the researchers’ spin-out now receives an unusually large grant for conducting human clinical trials.

Two decades of persistent basic research have paved the way for this opportunity to test a new, promising cancer therapy drug concept. Three researchers from Rigshospitalet and the University of Copenhagen have launched the process through a spin-out that has managed to attract an unusually large investment of DKK 380 million. The aim is to conduct human clinical trials using a technology that appears to be able to improve the treatment of cancers which typically show poor prognoses in advanced stages. Examples include cancer in the connective tissue and bone cancer, which are difficult to treat.

The three researchers behind the new drug concept are Professor Niels Behrendt, Research Director Lars Henning Engelholm and Molecular Biologist Christoffer Nielsen from the Finsen Laboratory, Rigshospitalet and the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen.

Their drug concept is based on the protein uPARAP, which was discovered and cloned by Niels Behrendt and Lars Henning Engelholm in the late 1990s. At the time, they were researching cancer cells’ ability to spread and metastasise. They learned that the uPARAP receptor effectively helps cancer cells break down their surroundings.

‘We discovered that uPARAP was not just a promising target for cancer treatment, blocking the function of the receptor. It turned out that we might be able to hijack the receptor and force it to place drugs within the cancer cells following a Trojan Horse strategy. Here the receptor plays a vital role in ensuring that only cancer cells are affected. It has taken us longer than we expected to refine the technology, but the current data look very promising’, says Niels Behrendt.

High-precision antibodies

The treatment strategy is based on more than 20 years of research conducted in the Finsen Laboratory. Even in early studies, Niels Behrendt’s and Lars Henning Engelholm’s research groups managed to block the function of the uPARAP receptor, and in a study involving mice suffering from bone cancer they were able to prevent cancer-induced bone destruction.

Blocking the uPARAP function was not enough to cure the cancer, though, and the researchers therefore started looking for a technology that could successfully kill the cancer cells. In theory, antibody drug conjugates (ADCs) seemed to be a promising method for high-precision targeting of cancer cells. ADCs consist of a combination of targeted antibodies and highly potent chemotherapy agents whose toxic effect is not activated until they are inside the cancer cell and the cancer cell discovers the ADC molecules. This is why it is compared to a Trojan Horse; the cancer cells actively import the drug that then attacks them from within. Traditional chemotherapy also affects the healthy cells, whereas ADCs are often capable of killing cancer cells more effectively without causing severe side effects, because this form of treatment does not require large doses, Niels Behrendt explains.

Treatment for advanced cancer

The researchers showed that the ADC concept targeted at the uPARAP receptor was surprisingly effective, and they managed to cure all tumour-bearing mice in the first trial when treated with the first version of the uPARAP ADC.

Lars Henning Engelholm explains how the first trial showed that the uPARAP receptor was particularly active in connective tissue cancer cells and in specific brain cancers. Initially, their research has therefore focussed mainly on sarcomas, which is a rare form of cancer found in bones, muscles, connective tissue, fatty tissue, neurolemma and vessels.

’The past 20-30 years have not seen huge progress in treatment for patients with sarcomas. We have been researching this for many years now, and we believe we have developed an extremely promising technology that will improve treatment for patients with sarcomas significantly’, says Lars Henning Engelholm.

He explains how international collaborators who have used the new drug concept have also seen positive results, and there is therefore reason to believe that the technology will be able to improve the treatment of other cancers as well.

According to Lars Henning Engelholm, the prognoses for most of the cancers targeted by the new drug concept are usually poor.

‘If our discovery turns out to be able to help people suffering from these cancers, the many years of hard research will have been worth it’, says Lars Henning Engelholm.

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FACTS:

Investment in the spin-out Adcendo

The step from basic research and animal trials to human clinical trials requires large investments. For a number of years, Niels Behrendt, Lars Henning Engelholm and Christoffer Nielsen have been planning this step.

It began with a long process of basic development funded by the Novo Nordisk Foundation, among others, and patenting of the technology through Rigshospitalet and the University of Copenhagen. They then established the spin-out Adcendo, which in 2017 bought the rights to use the invention. The three researchers are part owners of the company, as is Director Henrik Stage who helped set up the company. Since then the researchers have been refining the drug concept, preparing it for human clinical trials.

Initially, Adcendo’s promising data and knowledge about the biology of the uPARAP receptor and the ADC technology meant that it was accepted into the start-up programme Creation House at the BioInnovation Institute which supports entrepreneurs. With the admission came a loan of DKK 10 million, consultancy and access to advanced laboratory facilities.

Now an investor syndicate has chosen to invest the large sum of DKK 380 million in Adcendo. The company will use the money to jump-start clinical trials of the new drug concept for cancer therapy.