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CAR-T-cells therapy is a type of immunotherapy that uses the patient’s own cells – T lymphocytes, but genetically modified to recognize and destroy cancer cells. Prof. dr hab. n. med. Sebastian Giebel, Head of the Clinic of Bone Marrow Transplantation and Oncohematology at the Institute of Oncology in Gliwice, President of the Polish Lymphoma Research Group explains what the innovative method of treatment consists of.
CAR-T-cells – what is it?
Each of us has T lymphocytes in the body – immune cells involved in protecting against cancer, among other things. However, sometimes, for various reasons, this protection becomes weaker. Cancer cells are spinning out of control, T cells don’t notice it. When there are a lot of cancerous cells, lymphocytes start to ignore them – you can say that they “dormant” and “pretend” that the cancer is gone. Natural protection cannot work anymore.
CAR-T-cells therapy aims to reprogram T lymphocytes and reset them to fight cancerby endowing them with genes that enable these cells to recognize cancer as an enemy and have the tools to fight it.
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Terapia CAR-T cells from the technical side
In practice, therapy with CAR-T cells consists in isolating T lymphocytes for reprogramming from the blood collected from the patient using laboratory methods. The obtained cell material is frozen and in this form it is sent to a specialized laboratory. There, after thawing, T lymphocytes are reprogrammed – their DNA contains a gene encoding a protein – chimeric antigen receptor CAR (chimeric antigen receptor) – thanks to which they gain the ability to recognize cancer cells.
To modify the genetic material of lymphocytes, a biological vector in the form of an inactive virus is used, which carries the gene into the cell. The viruses used to introduce the CAR gene into the T lymphocyte are safe for humans and serve only as the carrier of the gene of interest.
In order to maximize the therapeutic potential of these lymphocytes, they are additionally stimulated and multiplied – in laboratory culture. The therapeutic material prepared in this way is directed to the facility where the patient is treated – the lymphocyte donor, who will soon receive these cells back, but already in a reprogrammed version.
Before administering genetically modified lymphocytes, the patient receives treatments that suppress his immunity. This prepares the field for the reprogrammed CAR-T cells to function.
A patient prepared in this way is injected into the blood by modified T lymphocytes, which spread throughout the body, recognize cancer cells thanks to the CAR receptor on their surface and destroy them. As a result of contact with cancer cells, CAR-T cells multiply, which additionally strengthens and preserves the reaction.
Modified CAR-T cells can stay in the patient’s body for 3 years and therefore act as a living medicine, preventing the cancer from returning.
Polish experience with CAR-T-cells therapy
In Poland, the experience with the use of CAR-T cells for the treatment of lymphomas is not very large yet, as it is a new method of cancer therapy. The first such therapy was used at the end of 2019 in Poznań, and shortly thereafter – in Gliwice. Currently, six therapies with the use of CAR-T cells have been carried out in our country in two oncology centers – three patients were treated in Poznań and three – in Gliwice.
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The therapy with CAR-T cells is applied to patients who have not been successful in the traditional methods of cancer treatment applied before. These are patients with resistance to at least two lines of treatment. The prognosis in such cases is very bad – the chance of winning the fight against lymphoma in such patients does not exceed 10-15 percent. International experience shows that the implementation of CAR-T-cells therapy increases the chances to approx. 35%. – and this is a fundamental difference.
CAR-T Cells in the eye of the patient
CAR-T-cells therapy was performed on a 62-year-old patient diagnosed with lymphoma. The treatment was carried out at the turn of 2019 and 2020 at the National Institute of Oncology in Gliwice.
Comments from the patient of Jadwiga Szotek:
«I have been feeling unwell since 2018 – for almost a year everything hurt, especially my leg. I had trouble walking, I couldn’t sit. Since I have Lyme disease, I was referred for further tests, but they (including computed tomography) did not indicate the cause. It wasn’t until the MRI showed that I had changes. Meta changes due to lymphoma or myeloma were suspected. In March 2019, type B lymphoma was diagnosed – it turned out to be a high-risk cancer.
Initially, I was given different combinations of chemotherapy over several series, but my body did not respond to the treatment. The disease progressed. Then I was offered a new treatment program – CAR-T-cells therapy, free of charge thanks to the so-called early access to medicine. This proposal fell to me, like an asterisk from the sky! I found out about the qualification for the therapy at the end of November 2019. In December 2019, cells were obtained from me, and on January 27, 2020, I was given a drip with modified T lymphocytes. It was a one-time infusion at the level of the collarbone, which lasted approx. 30 minutes.
Before therapy with CAR-T cells, I underwent many tests and consultations, incl. with a cardiologist and neurologist. My siblings were also examined for tissue compatibility – in case the CAR-T therapy was unsuccessful and it was necessary to genetic twin to obtain stem cells for bone marrow transplantation.
On the first day after the CAR-T cells were given, I felt fine, but the next day I developed a fever. Fever developed within the first week after the infusion.
In the second week I had problems with my memory – I forgot how to use the phone, I couldn’t cope with the TV remote control, I couldn’t read the text written on the piece of paper … Every day I was visited by doctors – specialists in neurology and psychology. I had to do memory exercises, such as counting or remembering words.
The beginning was really tough, but after two weeks everything gradually returned to normal. Now I have no problems with memory and coping with life. I have no problems with moving, although I still use a crutch and limp a little; and nothing hurts me.
My current well-being is 100 percent. better than last year. I have not been to the hospital since March 2020. Previously, hospitalizations took place every 2-3 weeks. I feel deeply that the CAR-T therapy has brought a positive effect – for sure. And I wish everyone would get it – for free, just like me. And that this treatment would help, as it helped me.
I am very pleased with this therapy. And I would like to thank the entire medical team from the National Institute of Oncology in Gliwice for their commitment and care for me. »
The article comes from the campaign “Hematology – learn about blood diseases” prepared by Warsaw Press. All materials can be found on http://hematologia.warsawpress.com/
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