The man rebuilding the body’s immune cells into cancer killers

Essand welcomes us to his lab at the Rudbeck Laboratory. Here, he and his team are developing ways to boost the body’s immune system to kill cancer cells. In particular, they work with white blood cells called T cells, which patrol the bloodstream and attack what they have learnt can make us sick.

“We take the patient’s T cells and give them a new receptor, a CAR, which stands for chimeric antigen receptor. This allows them to recognise tumour cells,” explains Essand, Professor at the Department of Immunology, Genetics and Pathology.

These CAR-T cells are already used in cancer care for certain types of leukaemia, lymphoma and myeloma. Essand and his team believe that their CAR-T cells are somewhat stronger and should be able to cure even patients who are not helped by existing treatments. This is because the CAR-T cells have been loaded with a little more ammunition in the form of an extra molecule.

“This means that, in addition to killing tumour cells, they can also activate the body’s immune system. We therefore gain something of a double effect is the idea,” he explains.

CAR-T cells against incurable brain cancer

The plan is to launch another clinical trial within two years. Patients with glioblastoma, a highly malignant and currently incurable brain cancer, will be treated with specially designed CAR-T cells.

Immunotherapies of various kinds are now increasingly taken for granted in cancer care. This was not the case when Essand started out on his career.

He obtained his doctorate in 1995 with a thesis on antibodies and cancer. This is a good example of the change that has taken place in the field – in line with the thinking at the time, his thesis looked at targeting antibodies at tumour cells. Today, most research focuses instead on immune cells, which Essand became interested in at an early stage.

“I worked on immunotherapy too when it wasn’t working in the 90s and early 2000s. Immunologists have always believed that the immune system could have some function against cancer, but oncologists were very sceptical,” he notes.

“Sounds lika a James Bond villain"

When Essand became Professor of Gene Therapy at the Department of Immunology, Genetics and Pathology in 2009, many people did not understand what he was doing.

“It was the first professorship in gene therapy in Sweden and at the time I got comments such as, ‘wow, that sounds a bit like a James Bond villain.’”

Suspicion of his field of research turned into appreciation more than a decade ago. This was namely when American researcher James Allison discovered that it was possible to block a system checkpoint in the body’s T cells, enabling them to fight cancer cells – a breakthrough that was rewarded with a Nobel Prize in 2018. Suddenly, immunotherapy became a major thing.

Molecular engineer

Essand likens himself to a molecular engineer. In addition to designing CAR-T cells, he also builds what are known as oncolytic viruses, which are modified to infect and kill cancer cells without damaging healthy tissue in the body. A study testing one of his oncolytic viruses in patients with neuroendocrine tumours, which can affect organs such as the lungs, pancreas and small intestine, will soon be completed.

One of the research colleagues with whom he works closely is his wife Anna Dimberg who, like him, is a professor at the Department of Immunology, Genetics and Pathology where she leads her own research group. Together they are also developing an entirely new form of gene therapy for glioblastoma.

“Unlike CAR-T cells that target tumour cells, the gene therapy we are developing is based on a viral vector that binds to tumour blood vessels and alters them. To create a viral vector, you start with a virus, but remove the disease genes in the virus and insert the gene you want to deliver. We are utilising the ability of the virus to enter specific cells,” explains Essand.

Hope for one of the really big breakthroughs

This is because cancerous tumours are masterful at protecting themselves against the body’s immune system. Among other things, blood vessels are altered and form around them, making it difficult for immune cells to penetrate. Previous treatments for tumour blood vessels have focused on cutting off the blood supply to the tumour.

Essand’s and Dimberg’s research project instead aims to open up the supply of T cells from the blood into the tumour. As blood vessels in different cancers behave similarly, the treatment could in theory work for most cancers. Essand and Dimberg hope that this could be one of the really big breakthroughs in cancer research.

But how does it work to both live together and work so closely together?

“It works really well. We are both so interested in research and are very curious, meaning we also understand that the other person sometimes gets bogged down and stuck into certain things,” he says.

Åsa Malmberg