Immunogenic Peptides for Tumour Control via CD4+ T Cell Activation
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Solution Overview
Problem
Current immunotherapy approaches for cancer treatment, particularly targeting tumour-specific antigens, have limited success and high relapse rates, with a focus on CD8+ T cells and MHC class I presentation, while the potential of CD4+ T cells through MHC class II presentation has been underexplored due to the belief that most tumours do not express MHC class II determinants and CD4+ T cells are not potent anti-tumour cells.
Innovation Solution
The use of isolated immunogenic peptides comprising a T-cell epitope derived from a tumour-associated antigen combined with a [CST]-(X)2-[CST] motif, specifically a C-(X)2-[CST] or [CST]-(X)2-C motif, to induce CD4+ regulatory T cells that are cytotoxic to cells presenting the tumour-associated antigen, potentially overcoming the limitations of existing therapies by targeting MHC class II presentation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy focuses on CD8+ T cells and MHC class I presentation, then tumour-specific antigen recognition is achieved, but treatment success is limited and relapse rates are high
Solution Approach 1:
The patent segments the immunotherapy approach by dividing the traditional single-pathway (CD8+ T cells only) into multiple pathways: activating both CD8+ T cells through MHC class I and CD4+ T cells through MHC class II presentation. This segmentation allows simultaneous engagement of different immune cell types to achieve more reliable tumour elimination and reduce relapse
Solution Approach 2:
The patent merges two previously separate immunotherapy pathways into a unified approach: combining MHC class I-restricted CD8+ T cell responses with MHC class II-restricted CD4+ T cell responses. This combination therapy integrates the cytolytic activity of CD8+ T cells with the helper and regulatory functions of CD4+ T cells, improving overall treatment efficacy and reducing relapse
2Adaptability or versatility
If CD4+ T cells are targeted through MHC class II presentation, then new anti-tumour mechanisms are activated, but this approach has been underexplored due to beliefs about tumour MHC class II expression
Solution Approach 1:
The patent inverts the conventional assumption that tumours do not express MHC class II molecules. By designing peptides that specifically target MHC class II presentation and demonstrating their efficacy, the patent challenges and reverses the established belief, opening new avenues for immunotherapy that were previously considered invalid
Solution Approach 2:
The patent changes the key parameter of MHC class expression consideration in tumour immunotherapy. Instead of assuming MHC class II absence or low expression, the patent designs and tests peptides optimized for MHC class II binding and presentation, thereby changing the fundamental parameter of antigen presentation pathway utilization and demonstrating enhanced anti-tumour immunity
Data Source
AI summary
The present invention relates to the use of immunogenic peptides comprising a T-cell epitope derived from a tumor-associated antigen and a redox motif such as C-(X)2-[CST] or [CST]-(X)2-C in the treatment of a tumor or in the treatment or prevention of a tumor relapse, and in the manufacture of medicaments therefore.