Cationic Antimicrobial Peptide for Tumour Immune Response
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Solution Overview
Problem
Current cancer treatments, such as cancer vaccines and immunotherapies, face limitations due to the lack of a strong immune response against tumour-specific antigens, primarily because of immune suppression mechanisms that inhibit effective immune activation against tumours.
Innovation Solution
Development of a peptide compound with specific characteristics, including a 9-amino acid sequence with 5 cationic and 4 lipophilic residues, optionally containing non-genetically coded amino acids, which disrupts tumour cell organelle membranes, releasing immunostimulatory agents and additional tumour-specific antigens, used in combination with a sub-cytotoxic chemotherapeutic agent to enhance immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer vaccines and immunotherapies are used to stimulate immune response against tumour-specific antigens, then immune activation is enhanced, but immune suppression mechanisms inhibit effective immune response
Solution Approach 1:
The peptide is designed with specific segmentation of amino acid types (5 cationic and 4 lipophilic residues in a 9-amino acid sequence) to separately target different aspects of the problem: cationic residues interact with negatively charged organelle membranes while lipophilic residues facilitate membrane penetration, together overcoming immune suppression while maintaining immune response effectiveness
Solution Approach 2:
The invention creates a composite functional molecule combining cationic and lipophilic amino acid residues in a specific arrangement, forming a peptide with dual functionality that can both disrupt organelle membranes and preserve immune response, effectively addressing the contradiction between immune activation and immune suppression
2Measurement precision
If tumour-specific antigens are isolated and synthesized in vitro for vaccine administration, then specific immune response is targeted, but the process is costly and time consuming
Solution Approach 1:
The peptide leverages the tumour's own organelles and antigens as the therapeutic agent. By disrupting organelle membranes, the peptide causes release of endogenous tumour-specific antigens and immunostimulatory agents that naturally exist within the tumour cells, eliminating the need for external antigen isolation and synthesis while maintaining high specificity
Solution Approach 2:
The peptide acts as an intermediary that facilitates the release of tumour-specific antigens from within the tumour cells themselves. Rather than requiring external antigen preparation, the peptide mediates the natural release of antigens through organelle membrane disruption, making the tumour's own components the therapeutic payload
3Reliability
If cationic antimicrobial peptides disrupt organelle membranes to release immunostimulatory agents, then immune response is enhanced, but tumour cell death mechanisms may be activated
Solution Approach 1:
The peptide is designed to exert partial action by selectively disrupting specific organelle membranes (such as mitochondria and lysosomes) without causing complete cell lysis. This partial membrane disruption is sufficient to release immunostimulatory agents and tumour antigens while preserving tumour cell integrity, thereby enhancing immune response without triggering excessive tumour cell death that would reduce immunogenicity
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 peptide compound induces a potent immune response against tumours, leading to synergistic effects in combination therapies, effectively inhibiting tumour growth and metastasis with reduced side effects, and can induce adaptive immunity against further tumour development.
Implementation Method 1
peptide compound with specific characteristics, including a 9-amino acid sequence with 5 cationic and 4 lipophilic residues, optionally containing non-genetically coded amino acids, which disrupts tumour cell organelle membranes
Data Source
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AI summary
The present invention provides a compound, preferably a peptide, having the following characteristics: a) consisting of 9 amino acids in a linear arrangement; b) of those 9 amino acids, 5 are cationic and 4 have a lipophilic R group; c) at least one of said 9 amino acids is a non-genetically coded amino acid (e.g. a modified derivative of a genetically coded amino acid); and optionally d) the lipophilic and cationic residues are arranged such that there are no more than two of either type of residue adjacent to one another; and further optionally e) the molecule comprises two pairs of adjacent cationic amino acids and one or two pairs of adjacent lipophilic residues; for use in the treatment of a tumour by combined, sequential or separate administration with a cytotoxic chemotherapeutic agent that inhibits immune tolerance, wherein the chemotherapeutic agent is administered at a sub-cytotoxic dose. The present invention further provides pharmaceutical packs or compositions comprising these active agents and methods of treating a tumour comprising administration of these active agents.