Blood cancer is defeated
Two patients were cured with their own cells
RIA Novosti, Vladislav Strekopytov.
The first two people with leukemia are officially recognized as completely cured by the experimental method of CAR-T-cell immunotherapy. The procedure was performed ten years ago. After that, both cancer cells disappeared and did not appear again. About the essence of the method and the history of two recovered patients — in the material of RIA Novosti.
"Live" medicine
For many decades, cancer has been treated with a standard set: surgery, radiation and chemotherapy. In recent years, immunotherapy has been added — this is when the body's own protective system is used to combat the disease.
When ingested by a foreign potentially dangerous substance — an antigen — the body produces antibodies. To identify antigens on the surface of immune cells, there are special protein complexes — T-cell receptors (TCR). Interacting with antigen molecules, TCR activates T-lymphocytes. This is the mechanism of the immune response.
The problem is that cancer cells are able to disguise themselves well. Natural T-cell receptors often do not notice them, which allows the tumor to grow freely. A few years ago, scientists developed a technology for genetic modification of T-cells, which increases their efficiency.
Blood is taken from the patient and T-lymphocytes are isolated from it. A gene encoding receptors for specific cancer antigens is embedded in them. T cells with artificial, chimeric antigen receptors (CAR-T cells - Chimeric antigen receptor T cells) are grown in the laboratory and injected back into the patient.
The scheme of immunotherapy of cancer with CAR-T cells
That is, the patient's own immune cells are reprogrammed outside the body in order to target them for certain types of cancer. The sequence encoding the CAR protein is usually delivered by a viral vector, although recently an mRNA platform has been used.
The advantage of CAR-T cells compared to other traditional immunotherapy agents, such as monoclonal antibodies or small molecules, is that they do not disappear over time, but, on the contrary, multiply, gradually replacing the rest of the white blood cells.
However, so far, immunotherapy with CAR-T cells is used only for the treatment of blood cancer, and then with great caution. Firstly, because serious complications in the form of cytokine release syndrome are possible. This happens when tumor cells have the same target antigens as healthy ones. Doctors are able to suppress this syndrome, but patients should be under constant supervision. Secondly, the method is relatively new, and long-term observations are needed to confirm the effectiveness. Now this gap has been filled to a certain extent.
Long-term effect of therapy
In a recently published article in the journal Nature , scientists from The University of Pennsylvania reported that two patients with blood cancer who received experimental CAR-T-cell therapy ten years ago are completely healthy.
Both suffered from lymphocytic leukemia, a chronic blood cancer that affects B-lymphocytes — white blood cells necessary for the production of antibodies. In 2010, they underwent a course of immunotherapy with CAR-T cells. Remission came pretty quickly. However, it was unclear how long the modified cells would last in the body, preventing the cancer from returning.
The patients were regularly tested. The University of Pennsylvania even created a special laboratory. Scientists assumed that some of the CAR-T cells would gradually lose their ability to fight cancer. This natural process is called T-cell depletion.
But the number of T-cells with chimeric receptors in both did not decrease, but, on the contrary, increased. In one, after 1.4 years, 97.5 percent of lymphocytes accounted for CAR-T cells, after 3.4 years - 99.6, and after that the indicator did not decrease. For the second, it was stable at 97.6 percent.
At the same time, in the early stages, T-killers (CD8+ CAR-T cells) prevailed among the modified cells, destroying cancer cells, and then a stable population of T-helpers (CD4+ CAR-T cells) was formed.
They were periodically extracted from the blood of patients and placed in Petri dishes along with cancerous ones. Only after making sure that CAR-T cells are active and do not disappear, the researchers announced the final cure of the patients.
Prospects of the method
It has been a long-standing dream of cancer scientists to create a simple non—invasive method of immunotherapy as an alternative to the complex and risky method of stem cell transplantation — the last hope of patients with severe blood cancer. These were the two volunteers who took part in the study.
In 1996, biochemist Doug Olson was 49 years old when he was diagnosed with lymphocytic leukemia (a cancer that begins in the bone marrow and then passes into the blood). Despite some initial success with chemotherapy, by 2010 almost half of his bone marrow was affected. And he was offered to try a new method. The second patient, Bill Ludwig, has had the same diagnosis since 2000, in the summer of 2010 his disease was in the terminal stage.
The head of the study, MD Carl June with Bill Ludwig, one of the participants in the clinical trials at the Abramson Cancer Center in Pennsylvania / Doug Olson, the second patient to receive CAR-T cells, celebrates his 75th birthday with his family. Photo: Penn Medicine.
Chronic lymphocytic leukemia is the most common type of leukemia in adults. Usually doctors manage to improve the condition of patients, but only for a while. Eventually, cancer cells develop resistance to treatment and patients die.
"In 2010, we did not think at all that this method would become therapeutic. Now we can say that CAR-T cells really save patients," said the head of the study, Professor of immunology and oncology Karl Jun.
The U.S. Food and Drug Administration (FDA) has already approved a technique developed by Dr. Jun and co-authors for the treatment of five types of blood cancers, including acute lymphoblastic leukemia, follicular lymphoma and multiple myeloma. Thousands of patients have received this therapy over the past four years, and now scientists and clinicians are monitoring the evolution of immune cells in the blood of these patients. In Russia, the method is also used.
The authors of the study believe that in the next decade, with the help of CAR-T cells, it will be possible to effectively treat all types of blood cancer. There are already universal genetic modification technologies that allow CAR-T cells to bind to any cancer antigens in the blood with the help of special adaptive molecules acting as adapters.
The universal CAR-T cell can be used against various cancer antigens recognized by adaptive molecules. CC BY 3.0 / Dmitry Dzhagarov.
Clinical trials of CAR-T-cell therapy for the treatment of tumors of internal organs — prostate, brain, stomach or intestines are not so successful yet. Not all patients respond to treatment, in some an overactive immune response causes a severe toxic reaction and even death. Scientists explain this by the complex structure of solid tumors and the fact that such cancer cells have yet unknown mechanisms of evading the immune system.
Nevertheless, the success is obvious. Doug Olson is 75, he feels great. He is engaged in long-distance running and has already overcome six half marathons. Bill Ludwig, a retired correctional officer, traveled with his wife in a mobile home, waited for his grandchildren, but, unfortunately, died in 2021 due to complications caused by COVID-19.
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