Dietary Fucose Modulation of Tumor Immune Microenvironment
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Solution Overview
Problem
Current immunotherapies for melanoma, such as antibody-based treatments and adoptive cell therapies, have limited responsiveness and duration of response in patients, necessitating the development of new approaches to enhance immune responses against cancer.
Innovation Solution
Administration of fucose, in the form of L-fucose, D-fucose, fucose-1-phosphate, or GDP-L-fucose, to increase tumor-infiltrating lymphocytes and reduce myeloid-derived suppressor cells, combined with anti-tumor agents like checkpoint inhibitors, to enhance immune responses and treat cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current immunotherapies (antibody-based treatments and adoptive cell therapies) are used to treat melanoma, then immune responses are activated, but responsiveness and duration of response are limited
Solution Approach 1:
The patent changes the biochemical parameters of the tumor microenvironment by modulating fucosylation levels through dietary fucose supplementation. This alters the glycosylation state of proteins on tumor and immune cells, thereby changing immune cell recruitment, activation, and persistence without modifying the immunotherapy agents themselves
Solution Approach 2:
Fucose acts as an intermediary substance that mediates between the diet and the immune system. It modifies protein glycosylation patterns which in turn affect immune cell-tumor cell interactions, serving as a bridge that enhances the effectiveness of immunotherapies
2Quantity of substance
If fucose is administered to increase tumor-infiltrating lymphocytes, then immune response is enhanced, but treatment complexity increases
Solution Approach 1:
The body's own metabolic pathways are utilized to achieve therapeutic effects. Dietary fucose is naturally metabolized through existing fucokinase and GDP-fucose synthesis pathways, allowing the body to self-process the supplement without requiring complex delivery systems or advanced administration protocols
Solution Approach 2:
The patent changes the nutritional parameter of the diet (adding fucose) to achieve profound immunological effects. This simple parameter change in the diet translates to significant increases in tumor-infiltrating lymphocytes without complicating the treatment regimen
3Quantity of substance
If fucosylation is increased through dietary supplementation, then immune cell infiltration is enhanced, but detection and measurement of fucosylation levels becomes more challenging
Solution Approach 1:
The patent replaces complex biochemical assays with lectin-based detection methods. Lectins provide specific, high-affinity binding to fucosylated epitopes, enabling detection through simpler techniques like flow cytometry, immunohistochemistry, or ELISA that are more accessible than mass spectrometry or other sophisticated analytical methods
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method significantly increases tumor-infiltrating lymphocytes and reduces myeloid-derived suppressor cells, leading to enhanced immune responses and tumor suppression, with dietary fucose supplementation showing promise in improving the efficacy of existing immunotherapies.
Implementation Method 1
a lectin (such as, for example, Ulex europaeus agglutinin 1 (UEA1) or Aleuria aurantia lectin (AAL)) that recognizes the sugar modification of interest
Data Source
AI summary
Disclosed are methods for treating a cancer and/or enhancing immune responses to infiltration of tumors comprising administering to a subject a fucose. Also disclosed herein are methods of detecting the presence of a sugar-modified protein (i.e., a glycosylated protein).