Yeast-based vaccines as immunotherapy
AssigneeGlobeImmune, Inc.
InventorsAlex Franzusoff, Donald Bellgrau
Life of this patent
Estimating the term…
Abstract
Compositions and methods for treating and/or preventing a variety of diseases and conditions that are amenable to immunotherapy and, in one particular embodiment, compositions and methods for treating and/or preventing cancer in an animal are described. Specifically improvements related to the use of a yeast-based vaccine comprising a yeast vehicle and an antigen that is selected to elicit an antigen-specific cellular and humoral immune response in an animal, for use in prophylactic and/or therapeutic vaccination and the prevention and/or treatment of a variety of diseases and conditions are disclosed.
Claims114
A method to increase survival or reduce tumor burden in an animal that has cancer, comprising administering to an animal a composition that increases survival of the animal or reduces tumor burden in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer;
- and
- ii) a peptide linked to the N-terminus of the cancer antigen or immunogenic domain thereof the peptide consisting of between two and six amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof;
- wherein the first six amino acids of the fusion protein consist of an amino acid sequence of M-X2—X3—X4—X5—X6;
- (1) wherein M is methionine;
- (2) wherein X2 is any amino acid except glycine, proline, lysine or arginine;
- (3) wherein X3 is any amino acid except methionine, lysine or arginine;
- (4) wherein X4 is any amino acid except methionine, lysine or arginine;
- (5) wherein X5 is any amino acid except methionine, lysine or arginine;
- and
- (6) wherein X6 is any amino acid except methionine.
A method to inhibit tumor growth in an animal that has cancer, comprising administering to an animal a composition that inhibits tumor growth in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer;
- and
- ii) a peptide linked to the N-terminus of the cancer antigen or immunogenic domain thereof the peptide consisting of between two and six amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof;
- wherein the first six amino acids of the fusion protein consist of an amino acid sequence of M-X2—X3—X4—X5—X6;
- (1) wherein M is methionine;
- (2) wherein X2 is any amino acid except glycine, proline, lysine or arginine;
- (3) wherein X3 is any amino acid except methionine, lysine or arginine;
- (4) wherein X4 is any amino acid except methionine, lysine or arginine;
- (5) wherein X5 is any amino acid except methionine, lysine or arginine;
- and
- (6) wherein X6 is any amino acid except methionine.
A method to increase survival or reduce tumor burden in an animal that has cancer, comprising administering to an animal a composition that increases survival of the animal or reduces tumor burden in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer;
- and
- ii) a peptide comprising an amino acid sequence of M-A-D-E-A-P (SEQ ID NO:1), wherein said peptide is linked to the N-terminus of the cancer antigen or immunogenic domain thereof, the peptide consisting of between two and 200 amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof.
A method to inhibit tumor growth in an animal that has cancer, comprising administering to an animal a composition that inhibits tumor growth in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer;
- and
- ii) a peptide comprising an amino acid sequence of M-A-D-E-A-P (SEQ ID NO:1), wherein said peptide is linked to the N-terminus of the cancer antigen or immunogenic domain thereof, the peptide consisting of between two and 200 amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof.
A method to increase survival, reduce tumor burden, or inhibit tumor growth in an animal that has cancer, comprising administering to an animal a composition that increases survival of the animal or reduces tumor burden in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer, wherein the cancer antigen is a mutant protein encoded by a ras gene selected from the group consisting of:
- K-ras, N-ras and H-ras genes;
- and
- ii) a peptide linked to the N-terminus of the cancer antigen or immunogenic domain thereof, the peptide consisting of between two and 200 amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof;
- wherein the first six amino acids of the fusion protein consist of an amino acid sequence of M-X2—X3—X4—X5—X6;
- (1) wherein M is methionine;
- (2) wherein X2 is any amino acid except glycine, proline, lysine or arginine;
- (3) wherein X3 is any amino acid except methionine, lysine or arginine;
- (4) wherein X4 is any amino acid except methionine, lysine or arginine;
- (5) wherein X5 is any amino acid except methionine, lysine or arginine;
- and
- (6) wherein X6 is any amino acid except methionine.
A method to increase survival, reduce tumor burden, or inhibit tumor growth in an animal that has cancer, comprising administering to an animal a composition that increases survival of the animal or reduces tumor burden in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer, wherein the cancer antigen is EGF-R;
- and
- ii) a peptide linked to the N-terminus of the cancer antigen or immunogenic domain thereof, the peptide consisting of between two and 200 amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof
- wherein the first six amino acids of the fusion protein consist of an amino acid sequence of M-X2—X3—X4—X5—X6;
- (1) wherein M is methionine;
- (2) wherein X2 is any amino acid except glycine, proline, lysine or arginine;
- (3) wherein X3 is any amino acid except methionine, lysine or arginine;
- (4) wherein X4 is any amino acid except methionine, lysine or arginine;
- (5) wherein X5 is any amino acid except methionine, lysine or arginine;
- and
- (6) wherein X6 is any amino acid except methionine.
A method to increase survival, reduce tumor burden, or inhibit tumor growth in an animal that has cancer, comprising administering to an animal a composition that increases survival of the animal or reduces tumor burden in the animal, wherein the composition comprises:
- a) a yeast vehicle;
- and
- b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
- i) at least one cancer antigen or an immunogenic domain thereof expressed by the animal's cancer, wherein the cancer antigen is VHL (von Hippel's Lindau protein);
- and
- ii) a peptide linked to the N-terminus of the cancer antigen or immunogenic domain thereof, the peptide consisting of between two and 200 amino acid residues that are heterologous to the cancer antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the cancer antigen or immunogenic domain thereof
- wherein the first six amino acids of the fusion protein consist of an amino acid sequence of M-X2—X3—X4—X5—X6;
- (1) wherein M is methionine;
- (2) wherein X2 is any amino acid except glycine, proline, lysine or arginine;
- (3) wherein X3 is any amino acid except methionine, lysine or arginine;
- (4) wherein X4 is any amino acid except methionine, lysine or arginine;
- (5) wherein X5 is any amino acid except methionine, lysine or arginine;
- and
- (6) wherein X6 is any amino acid except methionine.
Dependencies are inferred from the claim text.