Fasting-mimicking diet promotes cancer-free survival in acute lymphoblastic leukemia models
Inventors
Longo, Valter D. • BUONO, ROBERTA
Assignees
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Publication Number
US-12285453-B2
Publication Date
2025-04-29
Expiration Date
Abstract
A method for treating leukemia and in particular, lymphoblastic leukemia is provided. The method includes a step of administering an FMD to a subject identified as having leukemia optionally in combination with a chemotherapeutic agent and/or an autophagy inhibitor.
Core Innovation
The patent describes a method comprising administering a fasting-mimicking diet to a subject having leukemia. The fasting-mimicking diet is formulated to provide different caloric intake on day 1 versus days 2, 3, 4, 5, and any additional days, with day 1 having a higher caloric amount than later days. The diet is also formulated to include restricted daily sugar and protein, and specified daily ranges for monounsaturated fats, polyunsaturated fats, and saturated fats.
The fasting-mimicking diet is formulated to provide at least 60% calories from fatty acids, and at least 50% of the calories from fatty acids are from coconut oil and tree nuts. The patent further describes ketogenic fasting-mimicking diets and a fasting-mimicking diet package including diet portions such as soups, nutrition bars, crackers, and drinks. The document describes that the diet package and diet preparation are based on subject weight, and includes micronutrient supplementation and cycling with a refeeding diet.
The patent describes treating lymphoblastic leukemia, including acute lymphoblastic leukemia and B-ALL, with fasting-mimicking diet in combination with other agents. The method includes administering an autophagy inhibitor during the fasting-mimicking diet and may include a chemotherapeutic agent administered during the diet administration. In described experiments using BCR/ABL syngeneic ALL models, fasting-mimicking diet combined with vincristine and autophagy inhibition is reported to increase cancer-free survival, promote cancer cell death, modulate autophagy markers including LC3B, beclin1, and p62, and alter immune response through T-cell phenotype changes, including reduced PD-1+ populations.
The patent reports that depletion of CD8+ T cells reverses the survival benefit, and it describes mechanistic evaluations including cell viability and cytotoxicity, apoptosis and autophagy pathway assessments, and RNA-seq and TCR/IG repertoire analysis. The document further describes additional biological markers such as CD3+CD8+ T cells and PD-1, and it reports analysis of immune repertoire clonotypes using described tools and software.
Claims Coverage
The independent claim covers administering a fasting-mimicking diet to a subject with leukemia with specific day-by-day caloric reduction, macronutrient limits, and fatty-acid heavy composition defined by coconut oil and tree nuts. The claim includes one principal independent set of quantitative diet constraints, and the family further refines the method through additional dependent claim features such as duration, per-pound/day caloric levels, meal components, and combinations with chemotherapeutic agents and/or autophagy inhibitors.
Day-by-day fasting-mimicking diet with restricted sugar, protein, and fat ranges
Administering a fasting-mimicking diet to a subject having leukemia, wherein the fasting-mimicking diet provides 800 to 1250 kcal on day 1 and 500 to 950 kcal on days 2, 3, 4, 5, and any additional days, less than 30 g of sugar for each day, less than 30 g of proteins for each day, 15-30 grams of monounsaturated fats for each day, 2-10 g of polyunsaturated fats for each day, and less than 12 g of saturated fats for each day, with carbohydrates on day 1 greater than the amounts provided for days 2, 3, 4, 5, and any additional days.
Fatty-acid heavy fasting-mimicking diet sourced from coconut oil and tree nuts
Formulating the fasting-mimicking diet to provide at least 60% calories from fatty acids and wherein at least 50% of the calories from fatty acids are from coconut oil and tree nuts.
Across the independent claim, the inventive coverage is directed to a fasting-mimicking diet for leukemia that uses a day-by-day caloric reduction pattern with restricted daily sugar and protein, specified fat subclasses, and a carbohydrates day 1 increase, together with a fatty-acid heavy formulation where coconut oil and tree nuts provide at least half of fatty-acid calories.
Stated Advantages
Increased cancer-free survival when fasting-mimicking diet is combined with vincristine and autophagy inhibition in described BCR/ABL syngeneic ALL models.
Promotion of cancer cell death in described experiments using fasting-mimicking diet with vincristine and autophagy inhibition.
Modulation of autophagy markers including LC3B, beclin1, and p62.
Alteration of immune response, including T-cell phenotype shifts and reduced PD-1+ populations, with a reported reversal of the survival benefit upon CD8+ T-cell depletion.
Documented Applications
Treatment of leukemia in a subject using a fasting-mimicking diet, including acute lymphoblastic leukemia and B-ALL in described BCR/ABL syngeneic ALL models.
Combination administration during the fasting-mimicking diet of a chemotherapeutic agent and/or an autophagy inhibitor, as described for vincristine and autophagy inhibition.
Use of ketogenic fasting-mimicking diets and a packaged set of diet portions (soups, nutrition bars, crackers, drinks) for administering the fasting-mimicking diet.
Cycling regimens involving a fasting-mimicking diet followed by a refeeding diet over multiple cycles, as described in the document.
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