Cleavable vaccine compositions and uses thereof and methods of making and using the same
AssigneeThe Regents of the University of California
InventorJohn M. Timmerman
Life of this patent
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Abstract
The invention relates to methods for making vaccines using linkages that are cleavable under lysosomal processing conditions, and vaccine compositions obtained therefrom. In some embodiments, the vaccines comprise a tumor antigen, an immunogenic carrier and a linker covalently linking the tumor antigen and the immunogenic carrier by a thio ether linkage. Vaccines of preferred embodiments can be used against a cellular proliferative disease that is characterized by the tumor antigen.
Claims16
A method of making a cancer vaccine which comprises
- conjugating an immunogenic carrier comprising keyhole limpet hemocyanin (KLH) with a partially-reduced tumor-specific idiotypic immunoglobulin using a linker comprising a first reactive moiety which is maleimide and a second reactive moiety under conditions which permit the formation of a thio-ether bond between the partially-reduced tumor-specific idiotypic immunoglobulin and the first reactive moiety and a covalent bond between the immunogenic carrier and the second reactive moiety to give the cancer vaccine,
- wherein the thio-ether bond between the linker and the partially-reduced tumor-specific idiotypic immunoglobulin is cleavable under lysosomal processing conditions, and
- wherein the tumor-specific idiotypic immunoglobulin is associated with a B-cell proliferative disease selected from the group consisting of B-cell lymphoma, leukemia, multiple myeloma and light chain amyloidosis.
A cancer vaccine comprising a partially-reduced tumor-specific idiotypic immunoglobulin conjugated to an immunogenic carrier comprising keyhole limpet hemocyanin (KLH) by a bifunctional linker having at least one thio-ether bond between a maleimide of the bifunctional linker and the immunogenic carrier or the partially-reduced tumor-specific idiotypic immunoglobulin, wherein the thio-ether bond is cleavable under lysosomal processing conditions, and
- wherein the tumor-specific idiotypic immunoglobulin is associated with a B-cell proliferative disease selected from the group consisting of B-cell lymphoma, leukemia, multiple myeloma and light chain amyloidosis.
A cancer vaccine which comprises
- a tumor-specific idiotypic immunoglobulin;
- an immunogenic carrier comprising keyhole limpet hemocyanin (KLH);
- a bifunctional linker having a first moiety which is maleimide and a second moiety;
- wherein the tumor-specific idiotypic immunoglobulin is conjugated to the immunogenic carrier by the bifunctional linker, and
- wherein the first moiety forms a thio-ether bond with the tumor-specific idiotypic immunoglobulin or the immunogenic carrier, said thio-ether bond is cleavable under lysosomal processing conditions, and
- wherein the tumor-specific idiotypic immunoglobulin is associated with a B-cell proliferative disease selected from the group consisting of B-cell lymphoma, leukemia, multiple myeloma and light chain amyloidosis.
Dependencies are inferred from the claim text.