WT1 Helper Peptide Combinations for CTL and Helper T-Cell Activation
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Solution Overview
Problem
Existing cancer vaccines fail to efficiently induce cytotoxic T cells (CTLs) and helper T cells, limiting their effectiveness in cancer immunotherapy.
Innovation Solution
Development of WT1 helper peptides and conjugates of cancer antigen peptides that include specific amino acid sequences to induce helper T cells, enhancing the immune response by identifying novel MHC class II epitopes and combining them with cancer vaccines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing cancer vaccines are used, then they can be administered to patients, but they fail to efficiently induce helper T cells and CTLs, limiting their effectiveness
Solution Approach 1:
The invention segments the WT1 protein into multiple specific peptide sequences (SEQ ID NOs: 1-20) that can be individually selected and combined. This segmentation allows for the identification of optimal helper T cell epitopes and CTL epitopes that can be used separately or in combination to overcome the limitations of whole protein vaccines.
Solution Approach 2:
The invention creates composite vaccine formulations by combining multiple WT1-derived peptide sequences with different functions (helper T cell epitopes and CTL epitopes) into single vaccine compositions. This composite approach ensures simultaneous activation of both helper T cells and cytotoxic T cells, thereby improving overall vaccine effectiveness.
2Productivity
If only killer peptides (MHC class I-restricted) are used in cancer vaccines, then CTLs can be induced, but helper T cells are not activated, limiting the enhancement of CTL function
Solution Approach 1:
The invention merges two previously separate vaccine strategies into a single unified approach: combining MHC class I-restricted killer peptides (for CTL induction) with MHC class II-restricted helper peptides (for helper T cell activation). The WT1-derived peptides are designed to simultaneously engage both MHC class I and MHC class II pathways, ensuring coordinated activation of both cell types.
Solution Approach 2:
The invention develops multi-functional peptide sequences from WT1 that can serve dual purposes: some peptides can act as both helper T cell epitopes and CTL epitopes, or can be used in combination to achieve both helper T cell activation and CTL induction. This multi-functionality allows a single vaccine formulation to address multiple immune activation requirements.
Data Source
AI summary
The present application relates to WT1 helper peptides consisting of an amino acid sequence of 9 to 30 amino acid residues including a sequence: KLSHL as part thereof, and combinations of a WT1 helper peptide and a conjugate of cancer antigen peptides.