When the immune system attacks cancer

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Is it possible to change the body's own immune cells so that they can attack aggressive cancer cells? CAR T therapy at the Medical Unit for Cell Therapy and Allogeneic Stem Cell Transplantation (CAST) does just that, with promising results. "This is highly specialized cancer care that means we can now cure cancers that we couldn't before", says Clinical Director Stephan Mielke.

Karolinska's first CAR T therapy was carried out in 2019. Today, more than 30 cancer patients have undergone the treatment, both children and adults, and children with lymphoma or lymphocytic leukemia. Almost all patients have been treated by the team led by Stephan Mielke, Professor and Clinical Director at CAST in cooperation with the departments of Hematology and Pediatric at Karolinska.

Stephan Mielke.

- CAR T therapy is a new type of therapy that did not exist before. What we do is we take immune cells, usually from the patient, and genetically alter them. We put them together with an antibody that can detect cancer molecules. When we then reintroduce them into the patient's body, they will seek out and attack the cancer.

Very simply, Stephan Mielke describes it as putting special glasses on the immune cells so they can find the cancer cells. In addition to searching for and attacking the cancer, immune cells also increase in number when they detect cancer cells.

- This causes an explosion of cells in the body, which also causes severe side effects. It can be a very tough treatment that also requires that patients receive intensive care during the acute phase, because the drug is so effective, says Stephan Mielke.

Quick results

The results of the treatment are usually seen quickly. On a return visit four weeks after discharge, the cancer has often disappeared or been significantly reduced. However, despite the good results, treatment is not for everyone. The patient must be in good enough shape to cope with the side effects. The patient must also be able to wait for the treatment for one month, which is the time it takes to produce the new immune cells.

- How we choose treatment during that month is extremely important. If the patient receives too much treatment, they will not be in good enough shape to complete the CAR T therapy, but if they receive too little treatment, there will be too much tumors, which is not good either.

In the future, Stephan Mielke and others aims to bring CAR T therapy earlier in the disease process, and one goal is to be able to treat solid tumors, as well. A study is currently underway in collaboration with the Phase 1 unit with a gene-modified TCR, which involves reprogramming immune cells to recognize mutations inside cells.

Long-term follow-up

Stephan Mielke stresses that CAR T therapy is still a new method and that long term effects are still unknown. Therefore patients need long-term follow-up for 15 years or more.

- We must be humble in the knowledge that we do not yet know everything. This is a drug therapy that is made of you, it lives inside you, is part of you and keeps the cancer under control.

Allogeneic stem cell transplantation and especially cell therapy are developing rapidly, but what Stephan Mielke would like to see is more effective implementation in clinical care.

- As things stand, we are a little too slow with implementation in Sweden. There is a lot of bureaucracy and we would need to translate innovation into healthcare much faster to treat more patients. I see the changes in my patients so quickly. Although the side effects maybe are severe, this treatment makes most of my patients laugh again and gives them their lives back, says Stephan Mielke.

FACTS

CAR stands for Chimeric Antigen Receptor. CAR T therapy has been approved standard care in Sweden since 2019. Professor Stephan Mielke was one of the first doctors in Europe to perform the treatment with second-generation CAR T cells in 2017 in Germany. Today, Karolinska University Hospital is one of Europe's leading hospitals in performing the treatment. We receive patients from all over the country and have close cooperation with other hospitals in Sweden that also perform the treatment, especially with Uppsala University Hospital (Akademiska Sjukhuset).

A study of next-generation CAR T cells, called TCR cells, is currently underway. The goal is to reprogram immune cells to recognize mutations inside cells, not just outside. The treatment with new TCRs has been tested, for the first time in the world, in some patients with solid tumors at Karolinska University Hospital.