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US 6,719,974 B1Granted
Heat shock protein-based vaccines and immunotherapies
AssigneeSloan-Kettering Institute for Cancer Research
InventorsJames E. Rothman, Franz Ulrich Hartl, Mee H. Hoe, Alan Houghton, Yoshizumi Takeuchi, Mark Mayhew
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Abstract
The present invention relates to methods and compositions for inducing an immune response in a subject, wherein the subject is administered an effective amount of a heat shock protein complexed to a hybrid antigen comprising an antigenic domain and a heat shock protein-binding domain. These methods and compositions may be used in the treatment of infectious diseases and cancers.
Claims44
A method of treating melanoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from melanoma and a binding domain that noncovalently binds to a eukaryotic hsp70 and comprises a heptameric region having the sequence motif HyXHyXHyXHy (SEQ ID NO:29) where Hy represents a hydrophobic amino acid and X is any amino acid, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic hsp70;
- wherein the hsp70 is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the hsp70 are combined in vitro under conditions wherein binding of the hybrid antigen to the hsp70 occurs to form a non-covalent hybrid antigen-hsp70 complex.
5 more elements
A method of treating melanoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from melanoma and a binding domain that comprises a hydrophobic peptide of 7-15 amino acids that non-covalently binds to a eukaryotic hsp70, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic hsp70;
- wherein the hsp70 is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the hsp70 are combined in vitro under conditions wherein binding of the hybrid antigen to the hsp70 occurs to form a non-covalent hybrid antigen-hsp70 complex.
5 more elements
A method of treating melanoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from melanoma and a binding domain that noncovalently binds to a eukaryotic heat shock protein selected from the group consisting of hsp70, hsc70, and BiP, and comprises a heptameric region having the sequence motif HyXHyXHyXHy (SEQ ID NO:29) where Hy represents a hydrophobic amino acid and X is any amino acid, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic heat shock protein;
- wherein the heat shock protein is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the heat shock protein are combined in vitro under conditions wherein binding of the hybrid antigen to the heat shock protein occurs to form a non-covalent hybrid antigen-heat shock protein complex.
5 more elements
A method of treating melanoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from melanoma and a binding domain that comprises a hydrophobic peptide of 7-15 amino acids that non-covalently binds to a eukaryotic heat shock protein selected from the group consisting of hsp70, hsc70, and BiP, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic heat shock protein;
- wherein the heat shock protein is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the heat shock protein are combined in vitro under conditions wherein binding of the hybrid antigen to the heat shock protein occurs to form a non-covalent hybrid antigen-heat shock protein complex.
5 more elements
A method of treating lymphoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from lymphoma and a binding domain that noncovalently binds to a eukaryotic hsp70 and comprises a heptameric region having the sequence motif HyXHyXHyXHy (SEQ ID NO:29) where Hy represents a hydrophobic amino acid and X is any amino acid, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic hsp70;
- wherein the hsp70 is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the hsp70 are combined in vitro under conditions wherein binding of the hybrid antigen to the hsp70 occurs to form a non-covalent hybrid antigen-hsp70 complex.
5 more elements
A method of treating lymphoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from lymphoma and a binding domain that comprises a hydrophobic peptide of 7-15 amino acids that non-covalently binds to a eukaryotic hsp70, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic hsp70;
- wherein the hsp70 is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the hsp70 are combined in vitro under conditions wherein binding of the hybrid antigen to the hsp70 occurs to form a non-covalent hybrid antigen-hsp70 complex.
5 more elements
A method of treating lymphoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from lymphoma and a binding domain that noncovalently binds to a eukaryotic heat shock protein selected from the group consisting of hsp70, hsc70, and BiP, and comprises a heptameric region having the sequence motif HyXHyXHyXHy (SEQ ID NO:29) where Hy represents a hydrophobic amino acid and X is any amino acid, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic heat shock protein;
- wherein the heat shock protein is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the heat shock protein are combined in vitro under conditions wherein binding of the hybrid antigen to the heat shock protein occurs to form a non-covalent hybrid antigen-heat shock protein complex.
5 more elements
The method of claim 36, wherein the hydrophobic amino acid is independently selected from the group consisting of tryptophan, leucine and phenylalanine.
A method of treating lymphoma, comprising administering to a subject an effective amount of a complex of:
- (a) a hybrid antigen comprising an antigenic domain of a tumor antigen from lymphoma and a binding domain that comprises a hydrophobic peptide of 7-15 amino acids that non-covalently binds to a eukaryotic heat shock protein selected from the group consisting of hsp70, hsc70, and BiP, wherein the antigenic domain and the binding domain are separated by a short peptide linker;
- and
- (b) the eukaryotic heat shock protein;
- wherein the heat shock protein is from the same species as the subject;
- wherein the antigenic domain is from a first source and the binding domain is from a second source different from the first source;
- wherein the binding domain, the short peptide linker, and the antigenic domain are covalently bound in vitro;
- and
- wherein the hybrid antigen and the heat shock protein are combined in vitro under conditions wherein binding of the hybrid antigen to the heat shock protein occurs to form a non-covalent hybrid antigen-heat shock protein complex.
5 more elements
Dependencies are inferred from the claim text.