Enhanced immunogenicity of tumor associated antigens by addition of alphaGal epitopes
The invention relates to methods and compositions for causing the selective targeting and killing of tumor cells. The present invention describes prophylactic or therapeutic cancer vaccines based on purified TAA proteins or TAA-derived synthetic peptides altered by chemical, enzymatic or chemo-enzymatic methods to introduce αGal epitopes or αGal glycomimetic epitopes, in order to allow for enhanced opsonization of the antigen by natural anti-αGal antibodies to stimulate TAA capture and presentation, thereby inducing a humoral and cellular immune response to the TAA expressed by a tumor. The animal's immune system thus is stimulated to produce tumor specific cytotoxic cells and antibodies which will attack and kill tumor cells present in the animal.
1. A method for inducing an antitumor immune response in a patient comprising administering to the patient an effective amount of an synthetic immunogen comprising a tumor associated antigen or an immunogenic fragment thereof known to be capable of eliciting tumor associated antigen specific CD4+ and/or CD8+ immune responses, which has been conjugated to at least one synthetic peptide of 1-20 amino acids in length chemically modified in vitro to include one or more αGal epitopes.
2. The method of claim 1 , wherein the tumor associated antigen or immunogenic fragment thereof is conjugated to said at least one peptide at its amino-terminus or carboxy-terminus.
3. The method of claim 1 , wherein the tumor associated antigen or immunogenic fragment thereof is conjugated to at least two of said peptides at both its amino-terminus and its carboxy-terminus.
4. The method of claim 1 , wherein said at least one peptide is conjugated to the tumor associated antigen or immunogenic fragment thereof by direct linkage to an amino acid selected from the group consisting of cysteine, lysine, serine, and threonine.
5. The method of claim 1 , wherein said at least one peptide is conjugated to the tumor associated antigen or immunogenic fragment thereof by direct linkage to the primary amino group at its amino-terminus.
6. The method of claim 1 , wherein said at least one peptide comprises an endopeptidase amino acid consensus sequence.
7. The method of claim 1 , wherein said at least one peptide comprises at least one acceptor amino acid of an αGal epitope selected from the group consisting of lysine, cysteine, homocysteine, serine, threonine and glutamine, at least one of which has been chemically modified in vitro to be linked to an αGal epitope.
8. The method of claim 1 , wherein said immunogenic fragment comprises 7-20 contiguous amino acids of the amino acid sequence of the tumor associated antigen.
9. The method of claim 1 , wherein the structure of said one or more αGal epitopes as conjugated to the tumor associated antigen or immunogenic fragment thereof is Galα(1-3)Galβ(1,4)GlcNAc-R; wherein R is the tumor associated antigen or immunogenic fragment thereof.