CSPG4 Consensus Antigen Vaccine Breaking Immune Tolerance
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Solution Overview
Problem
There is a need for vaccines targeting Chondroitin sulfate proteoglycan 4 (CSPG4) that can break tolerance and effectively treat or prevent tumor growth and metastasis, as existing technologies have limitations in addressing the overexpression of CSPG4 in cancer types with limited expression in normal tissues.
Innovation Solution
An immunogenic composition comprising a nucleic acid molecule encoding a peptide with a sequence having at least 90% identity to CSPG4, which can be administered to elicit both humoral and cellular immune responses, including neutralizing antibodies and CD8+ T cell responses, to target CSPG4, potentially used in combination with other cancer vaccines or therapeutics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a vaccine targeting CSPG4 is developed, then tumor growth and metastasis can be treated or prevented, but breaking tolerance requires overcoming existing immune tolerance mechanisms
Solution Approach 1:
The patent modifies the CSPG4 antigen sequence by introducing mutations at specific positions (e.g., amino acid changes at positions 1-20, 40-60, or 80-100) to create an immunogenic variant that differs from the native CSPG4 protein. These parameter changes in the antigen sequence enable the vaccine to break immune tolerance while maintaining tumor targeting capability, as the mutated regions are not recognized by tolerant immune cells but still bind to CSPG4-expressing tumors.
Solution Approach 2:
The patent employs asymmetric mutation strategies where specific regions of the CSPG4 protein are mutated while other regions remain unchanged. This creates an asymmetric antigen structure that can evade immune tolerance in certain epitope regions while maintaining functional binding to the native CSPG4 protein on tumor cells, thereby breaking tolerance without losing therapeutic effectiveness.
2Reliability
If CSPG4 is targeted for vaccine development, then cancer treatment potential is enhanced, but the complexity of designing and administering the vaccine increases
Solution Approach 1:
The patent divides the CSPG4 protein into multiple epitope regions (e.g., N-terminal, central, C-terminal segments) and introduces mutations in specific segments independently. This segmentation allows the vaccine design to focus on particular immunogenic regions while maintaining simplicity in the overall vaccine structure, reducing design complexity while enhancing treatment potential through targeted epitope modification.
Solution Approach 2:
The patent uses synthesized peptide versions of the mutated CSPG4 antigen that can be produced through standardized chemical synthesis methods. This copying approach allows the complex mutated protein structure to be replicated in a controlled manner for vaccine formulation, simplifying the administration process while maintaining the therapeutic potential of the mutated antigen sequences.
3Reliability
If the nucleic acid sequence is optimized for immunogenicity, then immune response strength is improved, but the sequence identity to native CSPG4 may be reduced
Solution Approach 1:
The patent applies local quality changes by introducing mutations only in specific local regions of the CSPG4 protein (such as epitope regions at positions 1-20, 40-60, or 80-100) while maintaining the overall sequence identity and structure of the native protein. This localized mutation strategy enhances immunogenicity in specific areas without significantly reducing overall sequence identity, thereby improving immune response strength while preserving manufacturing precision.
Data Source
AI summary
Provided herein is an immunogenic composition comprising a synthetic consensus antigen to chondroitin sulfate proteoglycan 4 (CSPG4) protein which is abundant in many cancers. Also disclosed herein is a method of treating a tumor associated pathology in a subject in need thereof, by administering the immunogenic composition to the subject.