T-killers (CAR-T therapy)

The main articles are:

• Human blood
• Cancer treatment

Killer T cells, or cytotoxic T cells, are white blood cells specializing in the defeat of viruses and tumor cells. There are about five million of them in one teaspoon of blood.

T-killers directly contact damaged cells and destroy them. Unlike NK cells, T-killers specifically recognize a specific antigen and kill only cells with this antigen. There are tens of millions of T-killer clones, each of which is "tuned" to a specific antigen.

In the video below, T-killers kill a cancer cell.

The mechanism of operation of these cells is interesting. Once the T-killer detects the cancer cell, the membrane "fingers" of the lymphocyte test it. After such "identification," the T-killer binds to the cell and injects poisonous proteins (shown in red in the video) into microtubules on its surface. Finally, the white blood cell punctures this surface, allowing the poisonous cargo to destroy the cancer cell.

History

2024

For the first time in history, sclerosis and myopathy were cured by donor cells

In early October 2024, Chinese researchers at the Naval Medical University in Shanghai reported that they had managed to cure autoimmune diseases for the first time in history with donor immune cells. This achievement is the first step towards the introduction of new methods of therapy for severe ailments.

Three patients reportedly received CAR-T cell therapy based on donor cells. Usually, this method involves the use of the patient's own cells, which are genetically programmed and then returned to the human body. In the new work, donor material was used: immune cells were previously modified using CRISPR gene editing, and then introduced into the body of patients.

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Nature

One of the patients was a 42-year-old woman with autoimmune myopathy, a disease in which skeletal muscle tissue is affected. In addition, men aged 45 and 57 with systemic sclerosis received the new therapy: it is a rare chronic autoimmune connective tissue disease, in which degenerative changes and scarring of the skin, joints and internal organs are observed, as well as pathological changes in blood vessels. After administration, T cells destroyed pathogenic B cells that provoked an autoimmune reaction in the body.

As a result, two months after treatment, the woman achieved complete remission, which, as of October 2024, lasts six months. Both men also experienced significant improvement in symptoms, including cessation of scar tissue formation. At the same time, none of the patients showed a pronounced inflammatory reaction, known as cytokine release syndrome, which is observed in some people with cancer who received CAR-T therapy.^[1]

Blokhin National Medical Research Center received expensive equipment for CAR-T therapy

The National Medical Research Center (NMSC) of Oncology named after N.N. Blokhin completed the installation and put into operation expensive equipment for the production of CAR-T cells. This became known on September 26, 2024. Read more here

The new CAR T cell therapy copes with lymphoma even after relapse. People are already recovering

In mid-July 2024, researchers at Stanford Medical University presented new data on CAR-T cell therapies that help some patients with intractable lymphoma even after relapse.

CAR-T cell therapy involves extracting a patient's immune cells, adding a gene that helps those cells attack a specific protein on the surface of lymphoma cells, and then returning the modified immune cells to the body. Using the first options for this type of therapy, the researchers were able to achieve tumor reduction or disappearance in about half of patients with large B-cell lymphoma who did not respond to standard chemotherapy. However, with the failure of CAR-T cell therapy, which was observed in about half of the patients, the cancer returned, and the prognosis was extremely unfavorable.

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Memorial Sloan Kettering Cancer Center

Using an approach in which the target of modified immune cells instead of the CD19 protein was the tumor protein CD22, the researchers were able to significantly improve the treatment outcomes of these patients: more than half of the 37 people who relapsed after the initial CAR-T cell therapy were able to achieve a complete response. Thanks to this, life expectancy after relapse rose from 6 months to at least two years after the new treatment.

Initially, the study took place from 2022 to 2024 entirely at Stanford University. In 2024, a larger second phase of the study was launched in several institutions. USA Six CAR-T cell therapies have already been approved for several types of lymphoma, multiple myeloma and acute lymphoblastic leukemia, four of these therapies use the CD19 protein as a target, two more target another protein on the cell surface called the B cell maturation agent. The favorable results of the study may be the basis for the approval of a new variant of CAR-T-cell therapy that affects the CD22 protein.

New immunotherapy provides 100% cancer remission in patients

On January 4, 2024, Swiss researchers from the Lausanne Federal Polytechnic School (EPFL) reported new advances in CAR-T cell therapy in the treatment of malignant tumors. Scientists have managed to achieve 100% cancer remission in patients. Read more here.

2023

CAR T therapy coped with lupus and other autoimmune diseases in all patients

On December 9, 2023, the American Society of Hematology (ASH) reported that CAR T therapy had achieved complete drug-free remission in patients with systemic lupus erythematosus and other autoimmune diseases. The findings may offer hope for safe and effective treatment for many people suffering from severe ailments.

CAR T therapy is originally designed to treat blood cancer, in which antibody-producing B cells start dividing uncontrollably. The technology is a method of treating cancer patients with the help of their own immune cells, which are specially modified in laboratory conditions. After infusion, these specially prepared cells function as a tumor-oriented drug.

CAR T therapy has achieved complete drug-free remission in patients with systemic lupus erythematosus and other autoimmune diseases

The aim of the new study was to investigate whether CAR T therapy is effective in autoimmune diseases. Such ailments develop due to the pathological production of autoimmune antibodies or the proliferation of autoaggressive clones of killer cells against healthy tissues of the body. Experts selected 15 patients with severe systemic lupus erythematosus, idiopathic inflammatory myopathy and systemic sclerosis. They received a single infusion of modified immune cells. After that, patients stopped taking immunosuppressants.

Three months after therapy, all patients with systemic lupus erythematosus achieved complete remission and showed no symptoms of the disease. Moreover, as noted, they do not require any additional treatment. People with myopathy who underwent therapy also achieved remission, whereas patients with systemic sclerosis showed significant improvement in symptoms without exacerbation of the disease.^[2]

Cases of cancer after CAR-T cell therapy

On November 28, 2023, the U.S. Food and Drug Administration (FDA) initiated a review in connection with the results of clinical studies related to CAR-T cell therapy. Reports suggest that the use of this method may provoke the development of additional malignancies as side effects.

CAR-T-cell therapy is a method of treating cancer patients with the help of their own immune cells, which are specially modified in laboratory conditions. After infusion, these specially prepared cells function as a tumor-targeting drug. By the end of November 2023, the FDA had approved six CAR-T methods: Abecma (idecabtagen vicleucel), Breyanzi (lysocabtagen maraleucel), Carvykti (cyltacabtagen autolecel), Kymriah (tisagenleukleucel), Tecartus (brexukabtagen autolecel) and Yescarta (axicolabtagel). They are designed to treat blood cancers, including lymphomas and some types of leukemia.

Use of CAR-T cell therapy may trigger additional malignancies

The FDA notice says the overall benefits of the listed products outweigh the potential risks from their use. Nevertheless, due to the likelihood of the development of secondary malignancies, the regulator conducts an additional safety check. Based on its results, conclusions will be made about the need to take certain measures.

It is noted that the greatest fears are caused by the Kymriah product of Novartis AG. The regulator's adverse events database indicates that this therapy is associated with much more frequent cases of malignancies than other similar treatments. By the end of November 2023, more than 10 thousand patients received Kymriah therapy, and Novartis did not reveal a causal relationship between the treatment and secondary malignancies.^[3]

2022: Unique CAR-T cell therapy in Russia, replacing toxic chemotherapy

As it became known in April 2022, the National Medical Research Center of Hematology and the Dmitry Rogachev National Medical Research Center of Hematology jointly conducted CAR-T therapy in a patient with mantle zone cell lymphoma (a variant of B-cell non-Hodgkin lymphoma). This is the first experience in Russia in using CAR-T as the first line (after targeted therapy) in an adult patient.

According to Kommersant, CAR-T cell therapy is a treatment method based on the use of the patient's own cells. T lymphocytes are extracted from the patient's body using apheresis, a technology that allows blood to be divided into components and a certain number of lymphocytes can be obtained. Their modification is then done so that they can recognize and attack the tumor cells and they are injected back into the patient's body.

A unique CAR-T cell therapy was carried out in Russia, replacing the toxic chemoterap

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The 68-year-old Russian was diagnosed with lymphoma from the cells of the mantle zone, the so-called blastoid version is an extremely aggressive course, explained Evgeny Zvonkov, head of the intensive high-dose lymphoma chemotherapy department of the National Medical Research Center of Hematology. Subsequently, genetic breakdowns associated with absolute resistance to standard chemotherapy were found. Because of this, doctors were forced to apply a targeted effect in the first line, which allows them to bypass the signaling pathway associated with a mutation in the TR53 gene.

According to Zvonkov, the drugs ibrutinib and venetoclax have minimal toxicity, but, as it turned out, are extremely effective.

A week later, almost nothing remained of the tumor, instead of 1.5 million white blood cells, 700 became, and the spleen, the size of which was 30 cm, became normal, platelets and hemoglobin recovered. Before us was actually a healthy person, - said Evgeny Zvonkov.

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