Construction and methods of use of a therapeutic cancer vaccine library comprising fusion-specific vaccines

Inventors

Artomov, Maksym • Frenkel, Feliks • Golubev, Igor • Zolotareva, Olga

Assignees

BostonGene Corp

Abstract

Methods described herein relate to constructing therapeutic fusion-specific vaccine libraries, selecting a therapeutic fusion-specific vaccine for a cancer patient, and/or constructing a de novo therapeutic fusion-specific vaccine for patients having a gene fusion that is absent from a fusion-specific vaccine library.

Core Innovation

The invention relates to therapeutic cancer vaccines that use fusion-derived neoantigen peptides, including TMPRSS2/ERG. It selects two or more TMPRSS2/ERG fusion-derived neoantigen peptides from a library consisting of a plurality of containers, each container containing a respective fusion-derived neoantigen peptide with a respective sequence set forth in SEQ ID NOs: 1-403. The method obtains information about a TMPRSS2/ERG gene fusion in a biological sample and information relating to one or more HLA alleles of the subject.

Selected TMPRSS2/ERG fusion-derived neoantigen peptides consist of amino acid sequences selected from the group consisting of SEQ ID NOs: 374-381. The method determines binding of the selected peptides to the one or more HLA alleles of the subject and selects at least one peptide for administration when the peptide is determined to bind to the one or more HLA alleles. The approach is directed to using the TMPRSS2/ERG fusion information together with the subject’s HLA alleles to choose fusion-derived neoantigen peptides that bind those HLA alleles.

The invention provides administration of a peptide vaccine comprising the selected TMPRSS2/ERG fusion-derived neoantigen peptide to the subject, followed by monitoring tumor growth or formation in the subject after administering the fusion peptide(s). The document also discusses fusion-focused embodiments that select fusion-breakpoint long peptides, derive predicted neoantigen peptides, and mention peptide–MHC class I binding, immunogenicity, population and patient coverage, and anchor-modified peptides.

Claims Coverage

The provided claim coverage includes one independent claim, supported by multiple dependent claims. The independent claim covers four inventive features: acquiring TMPRSS2/ERG fusion and HLA allele information, selecting specific fusion-derived neoantigen peptides from a container-based SEQ ID library, determining peptide binding to the subject’s HLA alleles and selecting a peptide for administration, and administering a peptide vaccine followed by monitoring tumor growth or formation.

Overall coverage centers on TMPRSS2/ERG fusion information and subject HLA allele information guiding library-based selection of specific fusion-derived neoantigen peptide sequences, followed by binding determination, administration as a peptide vaccine, and monitoring tumor growth or formation.

Stated Advantages

Documented Applications

No documented applications found