Brain Tumor Antigen Peptides for MHC-Specific Immunotherapy
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Solution Overview
Problem
Current treatments for gliomas, particularly glioblastoma, have low survival rates, and existing immunotherapy approaches face challenges in targeting tumor-associated antigens without causing collateral damage to normal tissues or autoimmunity.
Innovation Solution
The development of personalized peptides targeting brevican, neurocan, and aggrecan epitopes, designed to bind specifically to an individual's MHC alleles, eliciting T cell and B cell responses, and administered through various routes to induce immune responses against gliomas, including vaccination regimens and adoptive cell therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tumor-associated antigens are targeted to stimulate immune response, then immune response against tumor is improved, but collateral damage to normal tissue and autoimmunity occur
Solution Approach 1:
The patent segments the immune response targeting by identifying specific epitopes within tumor-associated antigens that are uniquely expressed or upregulated in tumor tissues. By focusing on specific peptide sequences (e.g., from brevican, neurocan, versican, aggrecan) rather than entire proteins, the immune response is directed precisely at tumor cells while sparing normal tissues that express lower or no levels of these specific epitopes.
Solution Approach 2:
The patent applies local quality by selecting epitopes that exhibit tumor-specific characteristics in terms of expression level and location. The chosen epitopes are those that are highly upregulated in glioma tissues compared to normal brain tissue, creating a local distinction that allows the immune system to differentiate between tumor and normal cells based on the density and presence of specific antigenic determinants.
2Measurement precision
If personalized peptides binding to individual MHC alleles are designed, then immune response specificity is improved, but manufacturing complexity increases
Solution Approach 1:
The patent identifies epitopes that can bind to multiple common MHC alleles, creating a universal peptide vaccine approach that can be applied to a broad population. By selecting epitopes with broad MHC binding promiscuity, the need for complete personalization based on each individual's specific MHC genotype is reduced, while still maintaining sufficient specificity to elicit effective immune responses across diverse patient populations.
Solution Approach 2:
The patent optimizes peptide sequences by modifying specific amino acid positions to enhance MHC binding affinity while preserving epitope recognition by T cells. Through systematic variation of peptide parameters (amino acid composition, length, sequence), the patent identifies optimal sequences that balance MHC binding strength with immunogenicity, reducing the need for extensive customization for each patient.
Data Source
AI summary
The present invention relates to the identification and use of tumor epitopes from subjects with brain cancer, and particularly to epitopes from brevican, neurocan, versican, and aggrecan and their use in formulating cancer vaccines for treatment of tumor patients. In some preferred embodiments the methods provide a means of identifying T cell epitopes in proteins upregulated in brain tumors and the selection of those peptides which can stimulate T cell responses in individual subjects with a particular combination of HLA alleles. It further identifies the T cell exposed motifs comprised in T cell epitopes and enables the design of peptides with alternative amino acids in positions other than the T cell exposed motifs. In preferred embodiments, the MHC I and MHC II alleles of the affected subject are determined, and peptides are selected which bind to their MHC molecules with a desired affinity to elicit stimulation.