Peptide-Induced NK Cell Activation for Exportin-1 Cancer
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Solution Overview
Problem
Current therapies for cancer associated with overexpression of exportin-1 lack effective mechanisms to activate natural killer (NK) cells for targeted killing of cancer cells.
Innovation Solution
Development of specific peptides that activate NK cell-mediated immunity by targeting KIR2DS2+ NK cells, which recognize exportin-1 overexpressing cancer cells, and their use in vaccine approaches or immunogenic compositions to drive activation and expansion of NK cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used for cancer associated with overexpression of exportin-1, then general cancer treatment is provided, but effective activation of NK cells for targeted killing of cancer cells is not achieved
Solution Approach 1:
The patent uses peptides as intermediary molecules that bridge NK cells and exportin-1 overexpressing cancer cells. These peptides specifically bind to KIR2DS2 receptors on NK cells and also interact with exportin-1 on cancer cells, enabling targeted activation. This intermediary approach resolves the contradiction by providing both reliable NK cell activation and cancer-specific targeting capability simultaneously.
Solution Approach 2:
The invention changes the molecular parameters by designing specific peptide sequences (XnAX2X1 where X1 is leucine or phenylalanine and X2 is alanine, threonine or serine) that have optimized binding affinity for KIR2DS2+ NK cells. This parameter optimization enables the peptides to selectively activate NK cells against exportin-1 positive cancer cells, achieving both high activation reliability and cancer-specific adaptability.
2Adaptability or versatility
If broad-spectrum NK cell activation is achieved, then protection against multiple diseases is provided, but specific targeting of exportin-1 overexpressing cancer cells is reduced
Solution Approach 1:
The patent applies local quality by designing peptides with specific amino acid compositions and structures that are optimized for binding to exportin-1 on cancer cells while also activating KIR2DS2+ NK cells. This localized molecular design ensures that the NK cell activation is specifically directed at exportin-1 overexpressing cancer cells rather than providing broad-spectrum activation, thereby achieving high targeting precision for the intended application.
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 peptides effectively activate NK cells to recognize and kill cancer cells overexpressing exportin-1, providing a novel therapeutic mechanism for cancers characterized by high exportin-1 levels, such as liver cancer, melanoma, and lymphoma, with potential applications in vaccine formulations and immunotherapy.
Implementation Method 1
The peptides effectively activate NK cells to recognize and kill cancer cells overexpressing exportin-1, providing a novel therapeutic mechanism
Implementation Method 2
NK cell-mediated killing of cancer cells that overexpress exportin-1
Data Source
AI summary
The invention relates to a method of treatment or prophylaxis of cancer, wherein the cancer overexpresses exportin-1, the method comprising the administration of: a peptide capable of activating NK cell-mediated immunity to cancer cells that overexpress exportin-1, the peptide comprising or consisting of the amino acid sequence XnAX2X1, wherein Xn is an amino acid sequence of between 5 and 12 residues, and X1 is any amino acid; or leucine or phenylalanine; and X2 is alanine, threonine or serine; or administration of one or more of a nucleic acid encoding the peptide; an immunogenic composition comprising the peptide; a complex comprising the peptide; a vesicle comprising the peptide or nucleic acid encoding the peptide; a dendritic cell comprising the peptide and/or comprising nucleic acid encoding the peptide; an activated NK cell, that has been activated by the peptide; or a virus or virus like particle comprising the peptide and/or comprising nucleic acid encoding the peptide.