FAP Immunogenic Peptides Breaking Tumor Microenvironment Tolerance
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Solution Overview
Problem
Current cancer therapies face challenges in effectively breaking the body's tolerance to the tumor microenvironment, particularly due to the overexpression of Fibroblast Activation Protein (FAP) in cancer-associated fibroblasts, which limits the efficacy of immune therapies and can cause toxicity with existing chimeric antigen receptor (CAR) treatments.
Innovation Solution
Development of an immunogenic composition comprising a nucleic acid molecule encoding a peptide with a high degree of identity to FAP sequences, which can be administered to induce an immune response and break tolerance to the tumor microenvironment, potentially combined with other cancer vaccines or therapeutics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chimeric antigen receptor (CAR) treatments targeting FAP are used, then tumor progression is slowed, but lethal toxicity occurs in some mouse strains
Solution Approach 1:
The patent extracts only the essential immunogenic elements of FAP (specific epitopes and linear peptides) while removing the harmful components of full-length FAP expression and CAR T cell therapy. This allows targeted immune activation against FAP without the toxicities associated with complete protein expression or CAR-mediated cytotoxicity.
Solution Approach 2:
The patent employs short-lived, degradable peptide sequences and linear immunogenic motifs that can be rapidly cleared from the system. These short peptide sequences (e.g., 10-20 amino acids) provide sufficient immunogenicity without the persistent toxicity of full-length proteins or CAR T cells, allowing for safer repeated administration.
2Reliability
If FAP-expressing cells are ablated, then tumor growth is attenuated, but the therapy becomes more complex
Solution Approach 1:
The patent extracts only the essential immunogenic elements of FAP (specific epitopes and linear peptides) while removing the harmful components of full-length FAP expression and CAR T cell therapy. This allows targeted immune activation against FAP without the toxicities associated with complete protein expression or CAR-mediated cytotoxicity.
Solution Approach 2:
The patent replaces complex mechanical/CAR-based cytotoxic systems with a simpler immunogenic peptide-based approach that activates the host's natural immune response. Instead of using CAR T cells or antibody-mediated cytotoxicity, the therapy uses peptide sequences to induce T cell and antibody responses that naturally target and eliminate FAP-expressing cells.
3Reliability
If the body's tolerance to the tumor microenvironment is broken, then immune therapy efficacy is improved, but safety concerns arise
Solution Approach 1:
The patent applies local quality by targeting specific epitopes and linear peptide sequences within FAP that are locally expressed in the tumor microenvironment. The peptides are designed to be specific to FAP's immunogenic regions, activating immune responses only where FAP is expressed, thereby breaking tolerance locally without causing system-wide toxicity.
Solution Approach 2:
The patent changes the parameters of FAP presentation by using processed peptide sequences rather than full-length protein. This alters the immunogenicity parameters to create stronger, more specific T cell and antibody responses while reducing the risk of off-target effects and toxicity associated with full-length FAP expression.
Data Source
AI summary
Provided herein is an immunogenic composition comprising a synthetic consensus FAP antigen. Also disclosed herein is a method of treating or preventing a tumor associated pathology in a subject in need thereof, by administering the immunogenic composition to the subject.