RhoC Peptide Multi-Epitope Vaccine for Metastatic Cancer
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Solution Overview
Problem
Current cancer treatments face challenges in effectively targeting metastasis, as most cancer vaccines are melanocyte-specific and do not induce significant immune responses in non-melanocyte tumors, and existing immunotherapies have shown limited clinical improvement due to immune escape mechanisms and heterogeneous expression of tumor antigens.
Innovation Solution
Development of MHC Class I and Class II restricted peptides derived from RhoC, which can elicit spontaneous T-cell responses, allowing for the design of multi-epitope vaccines that target multiple tumor antigens and induce immunity against subdominant and cryptic epitopes, including those expressed in metastatic cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If melanocyte-specific vaccines are used, then immune response is induced in melanoma, but the vaccine is ineffective in non-melanocyte tumors
Solution Approach 1:
The patent identifies RhoC as a universal tumor antigen expressed across multiple cancer types including melanoma, lung cancer, ovarian cancer, and breast cancer. By targeting RhoC instead of melanocyte-specific antigens, the vaccine achieves broad applicability across different tumor types while maintaining reliable immune response induction, as evidenced by T-cell responses in both HLA-A2 positive and negative patients
Solution Approach 2:
The patent segments the immune response strategy into two components: targeting dominant HLA-A2 restricted epitopes for reliable responses in HLA-A2 positive patients, and incorporating subdominant epitopes restricted by other HLA molecules to extend coverage to HLA-A2 negative patients. This segmentation approach resolves the contradiction by providing both reliability through dominant epitopes and versatility through multiple HLA restrictions
2Reliability
If vaccination with TAA-derived peptides is performed, then anti-tumor T-cell responses are induced, but clinical course is mostly not improved due to immune escape mechanisms
Solution Approach 1:
The patent employs a dynamic multi-epitope vaccine strategy that adapts to patient-specific HLA phenotypes. By incorporating multiple epitopes restricted by different HLA molecules (HLA-A2, HLA-B7, HLA-B35, etc.), the vaccine dynamically adjusts to the patient's immune system capabilities, preventing immune escape through antigen heterogeneity while maintaining reliable T-cell response induction
Solution Approach 2:
The vaccine composition is a composite of multiple peptide epitopes derived from different tumor-associated antigens including RhoC, MUC-1, and HER-2/neu. This composite approach ensures that even if tumor cells escape recognition of one epitope, other epitopes continue to elicit protective immune responses, thereby improving clinical outcomes
3Measurement precision
If peptides specific to particular HLA molecules are used, then T-cell response is specific and effective, but the peptide cannot be applied to individuals with different HLA phenotypes
Solution Approach 1:
The patent develops a universal multi-epitope vaccine strategy that functions across diverse HLA phenotypes by incorporating epitopes restricted by multiple common HLA molecules. The vaccine maintains T-cell response specificity for each HLA-restricted epitope while achieving versatility across HLA phenotypes through the combined effect of multiple epitopes, making it applicable to the majority of patients regardless of their specific HLA genotype
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AI summary
The present invention relates generally to the field of prophylaxis and therapy of metastatic cancer. In particular there is provided a protein; Ras Homology gene family, member C (RhoC) or peptide fragments thereof that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to use of RhoC or peptides derived thereof or RhoC specific T-cells for treatment of metastatic cancer. Hence, the invention in one aspect relates to RhoC specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. Also the use of RhoC and immunogenic peptide fragments hereof in cancer treatment, diagnosis and prognosis is provided.