Cyclin B1 Peptides for Broad HLA Class II Binding
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Solution Overview
Problem
Current cancer vaccines targeting cyclin B1 lack efficacy due to limited ability to induce a strong and broad CD4+ T cell response across diverse HLA class II molecules, leading to variable immune activation in individuals.
Innovation Solution
Identification and development of immunodominant CD4+ T epitopes from cyclin B1 peptides that bind to multiple HLA class II molecules, including the most frequent HLA-DRB1 alleles in the Caucasian population, to stimulate a robust and consistent CD4+ T cell response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cancer vaccines use conventional cyclin B1 peptides, then they can be administered to patients, but they fail to induce a strong and broad CD4+ T cell response across diverse HLA class II molecules
Solution Approach 1:
The patent identifies and uses universal HLA class II binding motifs that can bind to multiple HLA-DR, HLA-DQ, and HLA-DP molecules simultaneously. The selected peptides contain amino acid sequences that recognize conserved regions across different HLA class II alleles, enabling a single vaccine formulation to elicit T cell responses in individuals with diverse HLA backgrounds. This multi-functionality approach resolves the contradiction by making the vaccine effective across different patient populations without requiring personalized formulations.
Solution Approach 2:
The patent systematically varies peptide parameters including amino acid composition, length (15-25 residues), and binding affinity thresholds to optimize both HLA binding capability and T cell immunogenicity. By adjusting these parameters and selecting peptides with high binding affinity to multiple HLA class II molecules, the vaccine achieves reliable efficacy across diverse populations. This parameter optimization allows the same peptide set to maintain effectiveness regardless of individual HLA variability.
2Adaptability or versatility
If cancer vaccines target multiple HLA class II molecules, then they can stimulate broader immune response, but the complexity of identifying suitable peptides increases
Solution Approach 1:
The patent divides the cyclin B1 antigen into multiple overlapping peptide segments (15-25 amino acids each) to systematically identify regions containing universal HLA class II binding motifs. By segmenting the antigen and testing each segment's binding capability across different HLA molecules, the complex identification process becomes manageable and systematic. This segmentation approach allows researchers to identify effective peptides without having to test every possible sequence combination.
Solution Approach 2:
The patent performs preliminary in silico screening and in vitro binding assays to pre-identify peptides with high affinity for multiple HLA class II molecules before final vaccine formulation. This preliminary identification and validation of candidate peptides reduces the complexity of the overall development process by filtering out non-effective sequences early, allowing focus on a smaller set of proven candidates for clinical development.
3Reliability
If cancer vaccines induce strong CD4+ T cell response, then they can enhance tumor control, but variability in HLA class II molecules among individuals reduces response consistency
Solution Approach 1:
The patent employs peptides designed to bind universally across HLA-DR, HLA-DQ, and HLA-DP class II molecules, ensuring that the vaccine can activate CD4+ T cells in individuals regardless of their specific HLA genotype. This universal binding capability ensures consistent and strong T cell responses across diverse populations, resolving the contradiction between response intensity and response consistency by making the vaccine effective for all individuals rather than limited to specific HLA types.
Data Source
Figure 1A~1B
Figure 2A~2B
AI summary
The present invention relates to peptides comprising at least one CD4+ T epitope, which is immunodominant in vitro, of the cyclin B1 tumour antigen, said peptides being capable of stimulating a specific human CD4+ T lymphocyte response in subjects who have varied HLA II molecules, and to the use of these peptides as a cancer vaccine and as a reagent for the diagnosis of cancer or the immunomonitoring of the cellular response against cyclin B1 during cancer or during an anticancer treatment.