Arginase2 C-Terminal Polypeptides for Reversing Tumor Immune Suppression
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Solution Overview
Problem
Cancer cells suppress anti-tumor immune responses through increased arginase expression, leading to arginine depletion and inhibition of T-cell proliferation, which hampers effective immunotherapy.
Innovation Solution
Development of immunogenic polypeptides derived from the C-terminus of the transit peptide region of human Arginase2, specifically targeting positions 21-23 and potentially up to 50 amino acids, to stimulate immune responses against Arginase2-expressing cells, including MDSCs and tumor-associated macrophages, enhancing anti-cancer immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If arginase expression is increased in cancer cells and tumor-associated macrophages, then arginine depletion occurs leading to suppression of anti-tumor immune responses, but this same mechanism promotes tumor growth
Solution Approach 1:
The patent converts the harmful immunosuppressive effect of arginase into a beneficial therapeutic target by developing vaccines that induce anti-arginase immune responses. The arginase enzyme, which originally suppresses T-cell responses and promotes tumor growth, becomes the target of therapeutic intervention through peptide vaccination, transforming its harmful role into a basis for cancer therapy
Solution Approach 2:
The patent applies preliminary anti-action by pre-vaccinating patients with arginase-derived peptides before tumor progression occurs or as early intervention. The vaccine induces anti-arginase T-cell responses in advance, creating an immune readiness that counteracts the immunosuppressive effects before they can fully establish tumor-promoting microenvironments
2Object-affected harmful factors
If arginase depletes arginine in the tumor microenvironment, then T-cell proliferation is inhibited, but this creates an opportunity for immunotherapy targeting arginase
Solution Approach 1:
The patent extracts the immunogenic epitopes from the arginase enzyme structure, specifically identifying and isolating peptide sequences (such as residues 161-210 of human arginase 1 or corresponding regions in arginase 2) that can serve as vaccine antigens. This extraction creates discrete therapeutic agents that can be administered as peptides or fusion proteins, separating the therapeutic function from the original enzyme's metabolic role
Solution Approach 2:
The patent uses arginase-derived peptides as intermediaries between the immune system and the arginase enzyme. These peptides serve as mediators that present the arginase antigenic determinants to T-cells, bridging the gap between the tumor microenvironment's arginase activity and the host's adaptive immune response without requiring direct contact with the full enzyme
Data Source
AI summary
The present invention relates to novel polypeptides, which are derived from Arginase2. The invention also concerns uses of the polypeptides and compositions comprising the polypeptides.