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Publication Number
US-8647865-B2
Publication Date
2014-02-11
Expiration Date
Abstract
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.
Core Innovation
The disclosed invention identifies a promiscuous human prostatic acid phosphatase (PAP) CD4 T-cell epitope comprising amino acid residues 257–271 (SEQ ID NO:1; RLQGGVLVNEILNHM) that is presented by at least 15 different HLA-DRβ1 alleles across multiple DR serological families. The presentation is described as occurring in multiple HLA-DR and HLA-DQ contexts, supporting broad class II use for T-cell recognition. The epitope is presented as a broadly applicable CD4 helper epitope for PAP+ responses.
The core scope centers on isolated 15–18 aa PAP-derived peptides and fusion products formed by fusing the SEQ ID NO:1 peptide to a heterologous polypeptide via a peptide bond. The disclosure includes embodiments where the fusion is linked to a heterologous polypeptide such as GM-CSF, as well as recombinant constructs containing an isolated nucleic acid encoding the fusion polypeptide. Related embodiments include expression cassette, recombinant viral vector, host cell, and compositions comprising physiologically acceptable excipients.
The document states utility of the identified epitope and fusion products in inducing and/or detecting PAP-specific T-cell responses. Experimental support described includes peptide mapping and functional assays using IFNγ and granzyme B readouts, along with APC/ELISPOT-type monitoring and related measures of T-cell responses. The epitope is presented as a “universal” CD4 helper epitope suitable for PAP+ prostate cancer immunotherapy/vaccines, grounded in the broad HLA-DRβ1 allele presentation described.
Claims Coverage
The partial set provided includes one independent claim. It defines the main inventive subject matter as an isolated nucleic acid encoding a specific fusion polypeptide arrangement involving the SEQ ID NO:1 PAP-derived CD4 T-cell epitope and a heterologous peptide linked via a peptide bond.
Fusion polypeptide nucleic acid encoding SEQ ID NO:1 peptide and heterologous peptide via peptide bond
An isolated nucleic acid encoding a fusion polypeptide consisting of a peptide consisting of 15 to 18 amino acids and comprising the amino acid sequence of SEQ ID NO:1, fused to a heterologous peptide via a peptide bond.
The claim coverage is centered on nucleic acids encoding a fusion polypeptide where the PAP-derived SEQ ID NO:1 peptide is fused to a heterologous peptide by a peptide bond.
Stated Advantages
Broad presentation as a promiscuous PAP CD4 T-cell epitope across at least 15 different HLA-DRβ1 alleles and multiple DR serological families.
Broad applicability as a “universal” CD4 helper epitope for PAP+ prostate cancer immunotherapy/vaccines.
Ability to induce or detect PAP-specific T-cell responses using the described functional readouts (e.g., IFNγ and granzyme B).
Documented Applications
Use of the PAP-derived “universal” CD4 helper epitope and related fusion products for PAP+ prostate cancer immunotherapy/vaccines.
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