Current FDA-approved Chronic Lymphocytic Leukemia Therapy
The current FDA approved treatment for CLL is monoclonal antibodies as they can help natural killer cells access cancerous cells in the blood. Niacinamide is currently being used in a Phase II clinical trial to enhance the activity of natural killer cells.
The current FDA approved treatment for CLL is monoclonal antibodies as they can help natural killer cells access cancerous cells in the blood. Niacinamide is currently being used in a Phase II clinical trial to enhance the activity of natural killer cells. Monoclonal antibodies are drugs that are designed to copy the benefit of natural antibodies and their ability to fight off cancer and other illness. Side effects are considered mild: fatigue, nausea, diarrhea and skin rash. However, they can cause lung and intestinal inflammation which require steroids.
Blinatumomab attaches to T cells (top left) and cancer cells (top right), enabling T cells to find and destroy cancer cells (bottom right). During this process, T cells are activated, creating more killer T cells (bottom left).
How it works
Each antibody is coursing through the body detecting a unique target that’s on the surface of a cancer cell called an antigen. When an antibody finds its target, it binds with the antigen and helps the immune system kill the diseased cell.
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Combining monoclonal antibodies with Niacinamide, an natural agent to induce Natural Killer cell production.
In a phase 1 trial of nicotinamide-expanded allogeneic NK cells, monoclonal antibodies, and IL2, 11 of 19 patients with NHL demonstrated complete response, suggesting that supplementation with nicotinamide during ex vivo NK cell culture should be further investigated for the treatment of NHL. —Melissa Norton
Administration of haploidentical donor natural killer (NK) cells, rituximab, and IL-2 to patients with non-Hodgkin lymphoma (NHL) has been shown to be safe, but the objective response rate was low, suggesting that further strategies to improve NK cell engraftment and function are needed. (1)
- Cichocki F, Zhang B, Wu CY, Chiu E, Day A, O’Connor RS, Yackoubov D, Simantov R, McKenna DH, Cao Q, Defor TE, Janakiram M, Wangen R, Cayci Z, Snyder N, Kumar A, Grzywacz B, Hwang J, Geffen Y, Miller JS, Maakaron J, Bachanova V. Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma. Sci Transl Med. 2023 Jul 19;15(705):eade3341. doi: 10.1126/scitranslmed.ade3341. Epub 2023 Jul 19. PMID: 37467318.
Another approach is prevention: Niacinamide’s Redox potential can arrest cancer proliferation
Niacinamide is a common nucleotide also known as the amide form of vitamin B3 used to restore the redox balance between the folate cycle and Serine HydroxyMethyltransferase (SHMT). SHMT provides methyl groups to the nucleic acids, dUMP to dTMP in the presence of NADPH and serine, through the activities of mitochondrial serine hydroxymethyltransferase (SHMT2), thymidylate synthase (TYMS), and a novel human mitochondrial dihydrofolate reductase (DHFR). see image
Mitochondria are at the heart of a metabolic switch between cell differentiation, DNA methylation, reduced de novo nucleotide synthesis, and cell cycle arrest on the one hand, and dedifferentiation, demethylation, increased de novo nucleotide synthesis, and cell cycle entry on the other.
The importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power, aka redox potential.(2)
2. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria.
Anderson D.D., Quintero C.M., Stover P.J.
PMID: 21876188 PMCID: PMC3174652 DOI: 10.1073/pnas.1103623108
Proc. Natl. Acad. Sci. U.S.A. 108:15163-15168(2011)
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