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NAM does not affect the cleavage induced by CD62L activation. NK cells enriched from the peripheral blood of four healthy donors were cultured overnight under the indicated culture conditions. Cells were then collected and analyzed by flow cytometry to assess surface CD16 and CD62L. Representative flow cytometry plots (top) and cumulative data from all four donors (bottom) are shown. credit: scientific translational medicine (2023). DOI: 10.1126/scitranslmed.ade3341
Cancer patients appear to be benefiting from donor-derived natural killer cells in an experimental method of cancer treatment that involves an army of aggressive immune system warriors capable of targeting and destroying malignant cells. is.
The natural killer cells were pretreated with nicotinamide, a compound commonly known to most people as niacin, or B vitamins.3. This is a substance that has a special affinity for natural killer cells and enhances their ability to kill cancer. Once prepared in the laboratory, these natural killers can be released against formidable targets at any time. This evolving methodology has shown promise in preliminary studies aimed at forcing hard-to-treat blood cancers into remission.
Ahead of new research published in scientific translational medicine, attempts by other teams to use natural killer cell infusions as a treatment for leukemia, lymphoma, and other hematological malignancies have not always been effective. Doctors were facing a problem. Some people did not respond to investigational treatments offered after standard treatments had failed.
Now, with a unique take on this new cancer treatment, medical scientists in the University of Minnesota’s Division of Hematology, Oncology, and Transplantation have discovered a way to increase the effectiveness of natural killer cells and strengthen their role as therapeutic agents. devised. . This innovative approach increases the efficacy of natural killer cells and has brought remission to patients with otherwise refractory cancers.
“Adoptive transfer of allogeneic natural killer cells has shown promise in inducing remission in relapsed or refractory leukemia and lymphoma,” Dr. Frank Cichocki and colleagues wrote in the journal. “Strategies that enhance natural killer cell survival and function are needed to improve clinical efficacy. We found that natural killer cells cultured in vitro with interleukin-15, IL-15, and nicotinamide We demonstrated stable induction of l-selectin, an important lymphocyte adhesion molecule, for lymph node homing.”
Nicotimide helps the body convert food into energy and is chemically part of the coenzymes NAD+ and NADH, which are important in redox reactions throughout the body. Among these activities is the production of adenosine triphosphate, ATP, which facilitates cellular and metabolic processes.
In 1937, researchers discovered that a systemic disease known as pellegra was caused by niacin deficiency. This disorder is represented by the three D’s: dementia, diarrhea, and dermatitis. Without treatment, which consists of simply administering niacin, pellegra can be fatal.
The research team’s selection of nicotinamide as a natural killer cell enhancer shines a spotlight on this common water-soluble compound and how nicotinamide can enhance the anticancer activity of natural killer cells. has been demonstrated. These cells are lymphocytes and members of the innate immune system, which is the body’s first response to invasive disease. The job of natural killer cells is to help control cancer and invading microorganisms.
Meanwhile, scientists developing experimental treatments are simply enhancing these cells to attack cancer more efficiently. An innovative new approach to treating blood cancers could emerge if further trials prove the method is effective and give Minneapolis-based scientists confidence they are on the right track. I’m going to do it.
“We are using adoptive transfer of natural killer cells expanded ex vivo with IL-15 and nicotinamide in combination with monoclonal antibodies in patients with relapsed or refractory non-Hodgkin lymphoma and multiple myeloma. “We conducted the first human Phase 1 clinical trial to test it,” Cicchocki claimed.in scientific translational medicine.
In a small preliminary study, Cicchocki and colleagues found that nicotinamide not only increases the activity of natural killer cells, but also increases their survival in the bloodstream, not only hunting down cancer cells but also increasing the ability of these cells to survive. discovered that it strengthens the ability to easily destroy.
The combination of nicotinamide-enhanced natural killer cells and monoclonal antibody treatment was safe in 30 patients, including 20 with relapsed or difficult-to-treat non-Hodgkin lymphoma. Of the 19 patients with non-Hodgkin lymphoma, 11 had a complete response and three had a partial response within 28 days of treatment. The research team found that nicotinamide appears to protect natural killer cells from oxidative stress while enhancing their ability to travel to lymph nodes.
“Higher frequencies of CD62L were associated with elevated transcription factor forkhead box O1, or FOXO1,” Cichocki said, referring to CD62L, the homing molecule that directs natural killer cells to lymph nodes. As a transcription factor, FOXO1 is involved in the regulation of numerous genes involved in metabolism, cell cycle progression, and programmed cell death.
In cancer, FOXO1 primarily acts as a suppressor of malignant cells through its role in promoting programmed cell death, or apoptosis, and inhibiting cell cycle progression, angiogenesis, and metastasis.
“Nicotinamide promoted FOXO1 stability by preventing proteasomal degradation,” added Cichocki, lead author of the study. “Natural killer cells cultured with nicotinamide exhibited metabolic changes associated with increased glucose flux and protection against oxidative stress.”
Natural killer cells treated with nicotinamide in the lab also showed an increased ability to trigger inflammatory and toxic responses against cancer cells. Cichocki et al. concluded that their findings suggest that new transplant strategies should be further investigated in larger clinical trials.
For more information:
Frank Cichocki et al. Nicotinamide enhances natural killer cell function and leads to remission in patients with non-Hodgkin’s lymphoma. scientific translational medicine (2023). DOI: 10.1126/scitranslmed.ade3341
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