Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses
Inventors
WANG, Joshua Weiyuan • INGAVAT, Nattha
Assignees
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Publication Number
US-11285203-B2
Publication Date
2022-03-29
Expiration Date
Abstract
This invention relates to chimeric virus-like particles (VLPs) assembled from a polypeptide comprising a papilloma 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.
Core Innovation
The invention relates to a virus-like particle (VLP) comprising a papilloma virus L1 protein and at least one antigen comprising at least one T cell epitope. The at least one antigen is attached to the VLP, and the T cell epitope is from a human pathogen heterologous to the papilloma virus of the VLP.
The at least one antigen is conjugated to a cysteine, lysine, or arginine residue of the L1 protein. Release of the antigen from the VLP in a tumor microenvironment results in complexation of the antigen with a major histocompatibility (MHC) molecule present on a tumor cell surface, resulting in activation of T cells and thereby inhibiting growth of the tumor cell.
Claims Coverage
The consolidated content includes three independent claim themes. The inventive concept is a papilloma virus L1 VLP displaying heterologous human-pathogen T cell epitopes, conjugated to specified L1 residues, and configured for MHC-complex formation in a tumor microenvironment to activate T cells and inhibit tumor cell growth; a related method claim contacts tumor or cancer cells with an effective amount of the VLP composition.
Papilloma virus L1 VLP displaying heterologous pathogen T cell epitopes
A virus-like particle (VLP) comprising papilloma virus L1 protein and at least one antigen comprising at least one T cell epitope, wherein the T cell epitope is from a human pathogen heterologous to the papilloma virus of the VLP, and wherein the at least one antigen is attached to the VLP.
L1-residue conjugation and tumor microenvironment release enabling MHC complexation
The at least one antigen is conjugated to a cysteine, lysine, or arginine residue of the L1 protein, wherein release of the antigen from the VLP in a tumor microenvironment results in complexation of the antigen with a major histocompatibility (MHC) molecule present on a tumor cell surface resulting in activation of T cells, thereby inhibiting growth of the tumor cell.
Contacting tumor or cancer cells with an effective amount of the VLP composition
A method of inhibiting tumor growth, tumor progression, or tumor metastasis comprising contacting a tumor cell or cancer cell with an effective amount of a virus-like particle (VLP) composition, wherein the VLP comprises a papilloma virus L1 protein and at least one antigen comprising at least one T cell epitope, wherein the at least one antigen is attached to the VLP, wherein the T cell epitope is from a human pathogen heterologous to the papilloma virus of the VLP, and wherein the at least one antigen is conjugated to a cysteine, lysine, or arginine residue of the L1 protein.
Conjugation extent to L1 cysteine, lysine, or arginine residues
The VLP comprises papilloma virus L1 protein and at least one antigen comprising at least one T cell epitope, wherein the at least one antigen is attached to the VLP, wherein the T cell epitope is from a human pathogen heterologous to the papilloma virus of the VLP, wherein the at least antigen is conjugated to a cysteine, lysine, or arginine residue of the L1 protein, and wherein about 35 to 100 percentage of the cysteine, lysine, or arginine residue of the L1 protein are conjugated to an antigen.
Across the independent claims, coverage centers on a papilloma virus L1 VLP carrying a heterologous human-pathogen T cell epitope antigen attached to the VLP and conjugated to cysteine, lysine, or arginine residues of L1. Release in a tumor microenvironment drives complexation with an MHC molecule on tumor-cell surface to activate T cells and inhibit tumor cell growth, and a conjugation extent constraint of about 35 to 100 percent is included in the additional VLP independent claim.
Stated Advantages
Inhibiting growth of the tumor cell by activating T cells through MHC-complexation of released antigen in a tumor microenvironment.
Inhibiting tumor growth, tumor progression, or tumor metastasis by contacting tumor or cancer cells with an effective amount of the specified VLP composition.
Documented Applications
Tumor-directed immune redirection to inhibit tumor growth, tumor progression, and tumor metastasis.
Combination use with checkpoint inhibitors is discussed in connection with the VLP-based tumor inhibition approach.
Use as antigen-presenting cell/T-cell detection tools is discussed.
Use to elicit durable systemic immunity and to cross-redirect unrelated pathogen vaccine immunity is discussed.
Using a VLP composition to inhibit tumor growth, tumor progression, or tumor metastasis by contacting a tumor cell or cancer cell with an effective amount of the VLP.
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