Aldose Reductase Inhibitor and Checkpoint Blockade Combination
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer therapies, particularly immune checkpoint inhibitor therapies, have limited efficacy and are associated with significant immune-related adverse events, necessitating the development of combination therapies that enhance anti-cancer effects while minimizing side effects.
Innovation Solution
Combining aldose reductase inhibitors, such as fidarestat, with immune checkpoint inhibitors, like anti-PD1 antibodies, to regulate CD8+ T cells and NK cells, thereby increasing the therapeutic potential of immunotherapy and reducing toxicities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitor therapy is used to treat cancer, then anti-cancer effects are achieved, but immune-related adverse events occur
Solution Approach 1:
The patent segments the immune system into different cell types (CD8+ T cells, NK cells, regulatory T cells) and targets them selectively through combination therapy. By using aldose reductase inhibitors alongside immune checkpoint inhibitors, the treatment selectively enhances anti-tumor immune cells while suppressing regulatory T cells that cause adverse events, thereby resolving the contradiction between efficacy and side effects
Solution Approach 2:
The patent introduces aldose reductase inhibitors as intermediary agents that mediate between the immune checkpoint inhibitors and the immune system. These intermediaries modulate the immune response by affecting glucose metabolism in immune cells, thereby enhancing anti-tumor effects while reducing immune-related adverse events without directly targeting the checkpoint pathways
2Ease of manufacture
If current cancer therapies are used, then treatment is provided, but survival rate remains poor due to recurrence
Solution Approach 1:
The patent merges multiple treatment modalities including immune checkpoint inhibitors, aldose reductase inhibitors, and potentially other chemotherapeutic agents into a combination therapy regimen. This combination approach targets cancer through multiple mechanisms simultaneously, preventing recurrence and improving survival rates while maintaining treatment availability
Solution Approach 2:
The patent employs preliminary action by using aldose reductase inhibitors to pre-condition the immune system before administering immune checkpoint inhibitors. This preliminary modulation of immune cell metabolism enhances the subsequent effectiveness of checkpoint blockade therapy, leading to better long-term outcomes and reduced recurrence
3Productivity
If immunotherapy is used to treat cancer, then dramatic responses are achieved, but immune-mediated side effects occur
Solution Approach 1:
The patent applies local quality by creating different immune microenvironments through selective modulation. Aldose reductase inhibitors create a favorable local quality in tumor-infiltrating lymphocytes by enhancing their metabolic function, while simultaneously creating an unfavorable local quality in regulatory T cells by impairing their suppressive activity, thereby achieving high therapeutic response with reduced side effects
Data Source
AI summary
Certain embodiments are directed to methods and compositions for treating cancer, specifically colorectal cancer by administering an aldose reductase inhibitor and an immune checkpoint inhibitor to a subject in need thereof. Certain embodiments are directed to methods of treating a subject having cancer comprising, administering (i) a composition comprising an aldose reductase specific inhibitor and (ii) a composition comprising an immune checkpoint inhibitor to the subject having melanoma, head and neck, or colorectal cancer.