Virus like particle comprising PD-1 antigen or PD-1 ligand antigen
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Publication Number
US-10464986-B2
Publication Date
2019-11-05
Expiration Date
Abstract
The present invention provides a virus like particle comprising a virus structural protein and an antigen derived from PD-1 or a ligand of PD-1, and a composition or kit comprising thereof, its use in immune response etc.
Core Innovation
The invention relates to a virus-like particle comprising a virus structural protein and an antigen selected from human Programmed Death-1 (PD-1), human Programmed Death-Ligand 1 (PD-L1), or human Programmed Death-Ligand 2 (PD-L2). The antigen is provided as a 10–300 amino acid fragment of the selected PD protein or as an amino acid sequence having at least 90% amino acid identity to the fragment.
In representative embodiments, the virus structural proteins are from alphavirus or flavivirus, including virus envelope proteins E1 and E2 and viral capsid. The antigen fragment is inserted into envelope protein E2, producing a virus-like particle architecture that combines the alphavirus/flavivirus structural proteins with a PD-1/PD-L antigen fragment.
The described system further provides nucleic acids, expression vectors, host cells, and pharmaceutical compositions for use in modulating PD-1–ligand interactions. The virus-like particle induces immunostimulation by producing an antibody against PD-1 or a PD-1 ligand and modulates immune response by inhibition of PD-1 activity and/or inhibition of the PD-1–ligand interaction, including PD-1–PD-L1 and PD-1–PD-L2 interactions.
Claims Coverage
The independent claim covers one overall inventive concept: a virus-like particle that couples a virus structural protein with a PD-1/PD-L antigen fragment meeting length and identity parameters. The dependent claim set further specifies alphavirus or flavivirus embodiments, capsid and E1/E2 arrangements, antigen insertion into E2, nucleic acids, pharmaceutical compositions, and treatment or prevention use.
Virus-like particle with PD-1/PD-L antigen fragments meeting length and identity
A virus-like particle comprising a virus structural protein and an antigen selected from human PD-1, human PD-L1, or human PD-L2, wherein the antigen comprises a 10–300 amino acid fragment or an amino acid sequence having at least 90% amino acid identity to the fragment.
Alphavirus or flavivirus structural protein selection
The virus structural protein is an alphavirus polypeptide or a flavivirus polypeptide.
Capsid and E1/E2 arrangement with antigen insertion into E2
A virus-like particle containing capsid protein and envelope proteins E1 and E2, wherein an antigen is inserted into E2.
Overall, the claim coverage centers on virus-like particles that present PD-1, PD-L1, or PD-L2 fragments using alphavirus or flavivirus structural proteins, including embodiments with antigen insertion into envelope protein E2. The dependent set extends this concept to nucleic acids, pharmaceutical compositions, and administration for immunostimulation through PD-1/PD-L interaction modulation.
Stated Advantages
Induces immunostimulation by producing an antibody against PD-1 or a PD-1 ligand.
Modulates an immune response by inhibiting PD-1 activity and/or the PD-1–ligand interaction, including PD-1–PD-L1 and PD-1–PD-L2 interactions.
Intended to treat or prevent cancer.
Intended to treat or prevent infectious disease.
Documented Applications
Treating or preventing cancer by administering the virus-like particle to a subject in need thereof to induce immunostimulation and modulate immune response through PD-1/PD-1 ligand interaction inhibition.
Treating or preventing infectious disease by administering the virus-like particle to a subject in need thereof to induce immunostimulation and modulate immune response through PD-1/PD-1 ligand interaction inhibition.
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