Polypeptides with affinity for heat shock proteins (HSPS) and HSP associated complexes (HACS) and their use in diagnosis and therapy

Inventors

Griffiths, Steven Gareth • Lewis, Scott Edwin

Assignees

Biosynth International Inc • LOOBAS Inc • ATLANTIC CANCER RESEARCH INSTITUTE • Vivitide LLC

Abstract

The present application is directed to a peptides comprising an a-helix forming-amino acid sequence that binds a heat shock protein. Also included is a polypeptide comprising (a) a first peptide portion that comprises an α-helix-forming amino acid sequence that binds a heat shock protein; and (b) at least one second peptide portion comprising an antigenic amino acid sequence and/or an a-helix-stabilizing amino acid sequence that increases the interaction of the first peptide portion with the heat shock protein. The present application also includes compositions comprising the peptides and/or polypeptides of present application and uses of the peptides and/or polypeptides of the present application for fractionating substances relevant for discovery, research or clinical analysis from a biological sample and as therapeutics.

Core Innovation

The invention relates to polypeptides that bind heat shock proteins and comprise an α-helix-forming amino acid sequence derived from myelin basic protein, including PSQGKGRGLSLSRFSWGA [SEQ ID NO 2:] or a sequence having one amino acid deletion, addition or substitution relative to [SEQ ID NO 2]. The polypeptides further comprise at least one second peptide portion that contains a tumour associated antigen (TAA) epitope of survivin at least 8 amino acids in length, or a sequence having one amino acid deletion or substitution relative to the survivin epitope.

The α-helix-forming myelin basic protein-derived portion and the survivin TAA epitope are provided as defined polypeptide constructs, including the ability to incorporate linkers and to present the peptide in labeled/immobilized formats. The constructs are described in association with affinity formats that enable capture of heat shock protein-associated material from biological samples.

The disclosed use is to affinity-associate and enrich heat shock protein-associated complexes (HACs) and related material, including cell-derived vesicles/exosomes, and then to analyze captured biomarkers for cancer and infectious disease detection. The disclosure further describes therapeutic and immunotherapeutic strategies, including inducing an immune response by administering an effective amount of one or more polypeptides to a subject in need.

Supportive findings in the disclosure include that MBP-derived fragments bind corynebacterial HSP70/HSP60 as demonstrated with CHIEF (counter HSP isoelectric focusing), that mass spectrometry identifies cancer-associated proteins captured by these complexes, and that intact mRNA is preserved in peptide-enriched vesicular material. The disclosure also reports anti-cancer effects in cell lines associated with the exemplified constructs.

Claims Coverage

The independent claim set covers polypeptides that combine an MBP-derived α-helix-forming region with a survivin tumour associated antigen (TAA) epitope, and also covers heat shock protein affinity complexes formed with the polypeptides. The independent claim(s) identify key inventive features including defined sequence constraints, survivin epitope requirements, and affinity association with heat shock proteins.

The core inventive concept is a defined polypeptide architecture that combines an MBP-derived α-helix-forming sequence with a survivin TAA epitope, and that forms affinity-associated complexes with selected heat shock proteins (HSP60/HSP70/HSP90/HSP27). The claims also cover immunological use by administering an effective amount of the polypeptide to induce an immune response in a subject in need.

Stated Advantages

Documented Applications