ANTIGEN PRESENTING CELL TARGETED CANCER VACCINES
First Claim
Patent Images
1. A fusion protein comprising the formula:
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Ab-(PL-Ag)x;
Ab-(Ag-PL)x;
Ab-(PL-Ag-PL)x;
Ab-(Ag-PL-Ag)x;
Ab-(PL-Ag)x-PL;
or
Ab-(Ag-PL)x-Ag;
wherein Ab is an antibody or fragment thereof;
PL is at least one peptide linker comprising at least one glycosylation site;
Ag is at least one cancer antigen; and
x is an integer from 1 to 20.
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Abstract
The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.
133 Citations
58 Claims
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1. A fusion protein comprising the formula:
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Ab-(PL-Ag)x;
Ab-(Ag-PL)x;
Ab-(PL-Ag-PL)x;
Ab-(Ag-PL-Ag)x;
Ab-(PL-Ag)x-PL;
or
Ab-(Ag-PL)x-Ag;wherein Ab is an antibody or fragment thereof; PL is at least one peptide linker comprising at least one glycosylation site; Ag is at least one cancer antigen; and x is an integer from 1 to 20. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21)
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20. An antigen delivery vector that expresses an anti-CD40 antibody or fragment thereof and two or more cancer peptides at the carboxy-terminus of the light chain, the heavy chain or both the light and heavy chains of the anti-CD40 antibody, wherein when two or more cancer peptides are present, the cancer peptides are separated by the one or more peptide linkers that comprise at least one glycosylation site.
- 22. An anti-CD40 fusion protein comprising an anti-CD40 antibody or fragment thereof and one or more cancer peptides at the carboxy-terminus of the anti-CD40 antibody, wherein when two or more cancer peptides are present the cancer peptides are separated by the one or more linker peptides that comprise at least one glycosylation site.
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26. A method of stabilizing cancer peptides comprising:
incorporating one or more cancer peptides that are unstable or insoluble into a fusion protein with an antibody, wherein the antibody and the cancer peptides are separated by one or more peptide linkers that comprise one or more glycosylation sites. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43)
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44. A method of enhancing T cell responses comprising:
immunizing a subject in need of vaccination with an effective amount of a vaccine comprising a fusion protein comprising an anti-CD40 antibody or portion thereof and one or more cancer peptides linked to the carboxy-terminus of the anti-CD40 antibody. - View Dependent Claims (45, 46)
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47. A method of making an anti-CD40-antigen fusion protein comprising:
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expressing a fusion protein comprising an anti-CD40 antibody or fragment thereof in a host cell, the fusion protein comprising one or more cancer peptides at the carboxy-terminus of the anti-CD40 antibody or fragment thereof, wherein when two or more cancer peptides are separated by one or more linkers, at least one linker comprising a glycosylation site; and isolating the fusion protein. - View Dependent Claims (48, 49, 50, 51, 52, 53, 54, 55)
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56. A method of expanding antigen-specific T cells in vitro comprising:
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isolating peripheral blood mononuclear cells (PBMCs) from a cancer patient; incubating the isolated PBMCs with an immunogenic amount of an α
CD40-(PL-Ag)x or α
CD40-(Ag-PL)x vaccine, wherein Ag is a tumor associated antigen and x is an integer 1 to 20;expanding the PBMCs in the presence of an effective amount of IL-2; harvesting the cells; and assessing the cytokine production by the cells to determine the presence of anti-cancer specific T cells.
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57. A tumor associated antigen-specific T cells made by the method comprising:
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isolating peripheral blood mononuclear cells (PBMCs) from a cancer patient; incubating the isolated PBMCs with an immunogenic amount of an α
CD40-(PL-Ag)x or α
CD40-(Ag-PL)x vaccine, wherein Ag is a tumor associated antigen and x is an integer 1 to 20;expanding the PBMCs in the presence of an effective amount of IL-2; harvesting the cells; and assessing the cytokine production by the cells to determine the presence of tumor associated antigen-specific T cells.
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58. A therapeutic vaccine comprising a fusion protein comprising the formula:
- Ab-(PL-Ag)x;
Ab-(Ag-PL)x;
Ab-(PL-Ag-PL)x;
Ab-(Ag-PL-Ag)x;
Ab-(PL-Ag)x-PL;
or Ab-(Ag-PL)x-Ag;
wherein Ab is an antibody or fragment thereof;
PL is at least one peptide linker comprising at least one glycosylation site;
Ag is at least one cancer antigen; and
x is an integer from 1 to 20.
- Ab-(PL-Ag)x;
Specification