Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses
AssigneePathovax LLC
InventorsJoshua Weiyuan WANG, Nattha INGAVAT
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Abstract
This invention relates to chimeric virus-like particles (VLPs) assembled from a polypeptide comprising a papilloma p virus (PV) L1 protein or L1/L2 protein and a target peptide comprising a CD8+ T cell epitope derived from a human pathogen. This invention also relates to methods using the chimeric VLPs as antigen-specific redirectors of immune responses.
Claims44
A chimeric virus-like particle (VLP), comprising a papilloma virus (PV) L1 protein and a surface-displayed target peptide wherein the target peptide comprises a CD8+ T cell epitope of a human pathogen, wherein the CD8+ T cell epitope is not a tumor associated antigen, wherein the target peptide is conjugated to the VLP and wherein the target peptide is not conjugated to the VLP via a polyionic:cysteine sequence.
A method for inhibiting the growth, progression or metastasis of a tumor in a subject comprising
- (a) ascertaining whether or not a subject in need thereof has been immunized or vaccinated against a pathogen,
- (b) administering a chimeric papilloma virus like particle (VLP) to the subject in an amount sufficient to inhibit the growth, progression or metastasis of the tumor,
- wherein the chimeric VLP comprises a papilloma virus L1 protein and a target peptide, wherein the target peptide is conjugated to a cysteine, a lysine or an arginine of the L1 protein, wherein the target peptide comprises a CD8+ T cell epitope of the pathogen against which the subject has been immunized and wherein the target peptide is surface-displayed on the chimeric VLP.
A method for inhibiting the growth of a cancer in a subject comprising
- (a) identifying the subject as a subject having a cancer,
- (b) identifying a vaccine comprising an antigenic agent that had been previously administered to the subject,
- (c) administering to the subject a composition comprising an effective amount of a chimeric VLP comprising a papilloma L1 protein and a target peptide, wherein the target peptide is conjugated to the L1 protein and the target peptide comprises a CD8+ T cell epitope of the antigenic agent in the vaccine which was previously administered to the subject,
- wherein the chimeric VLP is administered in an amount sufficient to stimulate an immune response in the subject comprising stimulating CD8+ T cells specific for the CD8+ T cell epitope of the antigenic agent and thereby inhibiting the growth of the cancer.
A method for inhibiting the growth of a cancer in a subject comprising
- (a) identifying the subject as a subject having a tumor,
- (b) administering a chimeric VLP to the subject in an amount sufficient to induce a cellular immune response by the subject to the target peptide,
- wherein the chimeric VLP comprises a papilloma L1 protein or L2 protein, or both and L1 and L2 protein, and a target peptide, wherein the target peptide is conjugated to a cysteine, a lysine or an arginine of the L1 or L2 protein, wherein the target peptide comprises a CD8+ T cell epitope that is not a tumor associated antigen from the tumor, and wherein the cellular immune response inhibits the growth of the tumor.
A composition comprising a population of chimeric VLPs, wherein each VLP comprises a papilloma virus L1 protein and a target peptide, wherein at least 30% of the cysteines or 30% of the lysines or 30% of both the cysteines and the lysines of the VLP are conjugated to a target peptide via a disulfide linkage, maleimide linkage or.
Dependencies are inferred from the claim text.