Promiscuous PAP CD4 T cell epitopes

Inventors

Wollan, Jami B. • Jones, Lori A.

Assignees

Dendreon Pharmaceuticals LLC

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 invention relates to an isolated PAP CD4 T-cell epitope that spans human prostatic acid phosphatase (PAP) residues 257-271 and is identified as SEQ ID NO:1 (RLQGGVLVNEILNHM). The epitope is described as an MHC class II-restricted CD4 helper epitope and as promiscuous across at least 15 HLA-DR alleles and across 9 HLA-DR serological families.

The described epitope enables broadly applicable CD4 helper targeting for PAP+ prostate cancer by engaging PAP-specific CD4 T-cell responses. The disclosure includes peptide formats spanning 15 to 20 amino acids and related embodiments for inducing and detecting PAP-specific T-cell responses. Antigen-presenting cells (APCs) and HLA-DR are used in the context of MHC class II restriction.

In addition to the peptide, the disclosure includes fusion constructs in which the peptide is combined with a heterologous polypeptide (e.g., GM-CSF). Further embodiments include isolated nucleic acids, expression cassettes, and host cell formats, as well as therapeutic/prophylactic compositions with physiologically acceptable excipients. The disclosure also describes functional readouts for PAP-specific T-cell responses, including IFN-γ/granzyme B readouts and example detection approaches such as ELISPOT, proliferation assay, and flow cytometry.

Claims Coverage

The independent claim identified in the provided claim set is directed to an isolated peptide defined by a specific 15-to-18 amino acid sequence. The main inventive features emphasized across the dependent claim set concern functional induction and detection of PAP-specific CD4 T-cell responses, breadth across multiple HLA-DR alleles or selected HLA-DR allele sets, and additional constructs and formulations.

The claim coverage centers on an isolated PAP CD4 T-cell epitope peptide defined by SEQ ID NO:1, with further coverage for PAP-specific T-cell immune response induction via antigen-presenting cells in an MHC class II context spanning at least 10 different HLA-DR alleles, including embodiments tied to an enumerated HLA-DR allele set. Additional coverage includes formulation as a composition with physiologically acceptable excipient, fusion constructs with heterologous peptides, and detection of the T-cell response using ELISPOT, proliferation assay, and/or flow cytometry.

Stated Advantages

Documented Applications