Promiscuous PAP CD4 T Cell Epitopes for Universal Prostate Cancer Immunotherapy
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Solution Overview
Problem
Current immunotherapies for prostate cancer are limited by the HLA-restriction of peptide epitopes, which confine their applicability to only a small percentage of the population, as they typically form productive peptide-MHC complexes with a small number of HLA alleles, restricting their use to individuals expressing those specific alleles.
Innovation Solution
Identification of novel promiscuous T cell epitopes in the human prostatic acid phosphatase (PAP) protein that can be presented by antigen-presenting cells expressing at least 15 different HLA-DRβ1 alleles, allowing for universal CD4 T helper cell epitopes in vaccines or immunotherapies for prostate cancer, specifically the peptide sequence of 257-271 (RLQGGVLVNEILNHM) which induces T cell activation across multiple HLA-DR alleles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional peptide epitopes are used in immunotherapies, then T cell responses can be induced in individuals with specific HLA alleles, but the applicability is limited to only a small percentage of the population
Solution Approach 1:
The patent identifies promiscuous T cell epitopes within the PAP protein that can be presented by multiple HLA-DR alleles simultaneously. This allows a single peptide vaccine composition to induce T cell responses across diverse HLA types, making the immunotherapy universally applicable to the general population rather than limited to specific HLA allele groups
2Reliability
If peptide epitopes are designed for specific HLA alleles, then strong T cell responses can be induced in matched individuals, but the device complexity increases to determine HLA typing and select appropriate epitopes
Solution Approach 1:
The patent extracts and identifies specific promiscuous epitope sequences from the PAP protein that inherently possess the ability to bind multiple HLA-DR alleles. By isolating these universal epitopes, the complex process of HLA typing and epitope matching is eliminated, as the same peptide composition can be used for all patients regardless of their HLA genotype
Data Source
AI summary
The present invention relates to the discovery of novel T cell epitopes of the human prostatic acid phosphatase (PAP) protein that is promiscuous for at least 15 different HLA-DR alleles. The invention also relates to compositions that contain one of the novel epitopes or a fusion peptide of such an epitope and a heterologous polypeptide. Further disclosed herein is the use of the epitopes or their fusion peptides, and compositions containing the epitopes or their fusion peptides.