Antibody developed in Denmark helps the body to fight cancer – University of Copenhagen

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22 June 2016

Antibody developed in Denmark helps the body to fight cancer

Danish researchers from the Faculty of Health and Medical Sciences (SUND) at the University of Copenhagen have developed an antibody that is so effective that it may prove to be the future drug against a large number of cancers as well as boosting the efficacy of new immunotherapies.

The antibody has been developed by the Copenhagen Center for Glycomics, the Department of Cellular and Molecular Medicine and the Department of Odontology at SUND and has been tested in a specific type of immunotherapy developed in collaboration with the University of Pennsylvania (UPENN), USA. The results have just been described in a scientific article in the recognised scientific journal Immunity (http://www.cell.com/immunity/home). 

The major advantage of the new antibody is that it recognises a cancer-specific change in an otherwise normal protein on the surface of cells in the body. The change occurs when shortened sugar molecules attach to the protein, and these are the molecules which the antibody developed in Denmark is specifically capable of recognising.

The antibody recognises and therefore only attacks cancer cells, thus allowing the researchers to now test new and very potent forms of treatment, which has so far not been possible with other types of antibodies. Antibodies can be attached to the body's own killer cells – the T cells, which then attack and kill the cancer cells.

"The antibody is grafted to T cells extracted from the patient. This means that the T cells can recognise the cancer, and when these antibody-loaded T cells are then returned to the patient's body, they track down the cancer cells and kill them," says Catharina Steentoft, Postdoc at the Copenhagen Center for Glycomics and co-author of the article in Immunity. 

A T cell grafted with cancer-targeting antibodies is called a CAR (Chimeric Antigen Receptor). The CAR method is extremely effective, but has had its limitations, because the loaded cell has killed more than just the cancer.

"The antibodies used so far have targeted much more than just the cancer. Their use has therefore been limited to a few cancer types," says Associate Professor Ulla Mandel, Department of Odontology, another co-author of the article.

Very few adverse reactions 
The team at the University of Copenhagen is working with one of the world's leading pioneers in the field: Carl June, Professor in Immunotherapy, University of Pennsylvania, who has previously used the CAR method to cure leukaemia – one of the few cancers for which it has so far been possible to use the method without severe adverse reactions.

The new experiments have been carried out in mice with pancreatic cancer, which, unlike, for example, leukaemia involves a solid tumour. The experiments showed that the tumours were inhibited significantly and, in many cases, disappeared altogether.

"The problem with the antibodies which have been available until now is that they have not only destroyed the cancer but normal tissue as well. But our antibody does not target the healthy cells," says Ulla Mandel, who originally developed the antibody and has worked on it for ten years.

Effective against many cancers
So far, the antibody has thus proved effective in mice, and even though there is a long way from mice to humans, the researchers are optimistic. 

"The method has been shown to be so good that we expect to perform experiments in humans within the next two years, and if everything goes according to plan, it may be introduced as a real treatment against cancer within the next five years," says Catharina Steentoft, which is currently a visiting researcher at Carl June's laboratory at UPENN.

And if the treatment proves to be as effective as the researchers hope, it will be possible to use it as a model for many different cancers.

"In simple terms, the antibody is based on a template, which means that we will be able to adapt it to also be used to treat a number of other cancers such as ovarian or breast cancer. We are in the process of establishing so-called cell display technologies to develop the next generation of antibodies," says Ulla Mandel. 

The University of Copenhagen has patented and owns the rights to the antibody, which may become a significant source of income for the university and the researchers if they succeed in designing a successful treatment for humans. We have already entered into a licence agreement with the Swiss company ADC Therapeutics, which is owned by AstraZeneca, concerning the use of the antibody for another type of cancer treatment, and this agreement is also expected to generate significant income.

The development of the new antibody at the Faculty of Health and Medical Sciences is supported by the Danish National Research Foundation and the Danish Council for Independent Research. 

You can read the entire article in Immunity here: http://www.cell.com/immunity/fulltext/S1074-7613(16)30202-3

Contact:  Catharina Steentoft (steentoft@sund.ku.dk, tel. +45 61675816) or Ulla Mandel (ulma@sund.ku.dk, tel. +45 35326637/+45 30226287)