Xenoantigen-displaying anti-cancer vaccines and method of making

1. A composition, comprising:

an antigen composition consists essentially of one of compounds 9, 17, or 21:

a xenoantigen composition comprising a second lipid moiety, a second linker moiety, and a xenoantigen moiety; and

at least one liposomal formulation, wherein the antigen composition and the xenoantigen composition are embedded in the liposomal formulation;

wherein:

the xenoantigen moiety contains a structure comprising: an α- or β-linked L-rhamnose epitope, a β-linked α-Gal disaccharide epitope, or an α- or β-linked Forssman disaccharide epitope:

and

the second linker moiety comprises a chain of C 1-m alkyl, dialkyl substituted aryl C 1-m alkyl, or —CH 2 CH 2 (OCH 2 CH 2 ) m —, wherein m is a positive integer.

2. The composition of claim 1 , wherein the second lipid moiety contains a structure of the Formula IX:

3. The composition of claim 1 , wherein the second linker moiety comprises a tetraethyleneglycol (TEG) of Formula VIII:

4. The composition of claim 1 , wherein the liposomal formulation comprises 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol in a ratio of from about 80:20 to about 70:30, respectively.

5. The composition of claim 1 , further including at least one immunologic adjuvant selected from the group consisting of: a saponin, monophosphoryl lipid A, 3-O-deacylated monophosphoryl lipid A, and interleukin 12.

6. A composition, comprising:

an antigen composition comprising a first lipid moiety, a first linker moiety, and an antigen moiety;

a xenoantigen composition comprising a second lipid moiety, a second linker moiety, and a xenoantigen moiety; and

at least one liposomal formulation, wherein the antigen composition and the xenoantigen composition are embedded in the liposomal formulation;

wherein:

the antigen moiety comprises a Pam 3 Cys-MUC1 VNTR-TACA conjugate;

the first lipid moiety comprises a Toll-like receptor (TLR) agonist ligand;

the first linker moiety comprises a chain of C 1-n alkyl, dialkyl substituted aryl C 1-n alkyl, or —CH 2 CH 2 (OCH 2 CH 2 ) n —, wherein n is a positive integer; and

the xenoantigen moiety comprises α- or β-linked L-rhamnose.

7. The composition of claim 6 , wherein the TACA comprises: TF, Tn, sialyl Tn (sTn), or sialyl Lewis a (sLe a ) antigens:

8. The composition of claim 6 , wherein the TACA comprises an autologous or heterologous helper T-cell epitope, wherein the autologous or heterologous helper T-cell epitope comprises a sequence expressed on a tumor cell.

9. The composition of claim 8 , wherein the autologous or heterologous helper T-cell epitope comprises a mucin 1 (MUC1) variable number tandem repeat (VNTR) having one of the following amino acid sequences:

PDTRPAPGST(Tn)APPAHGVTSA [SEQ ID NO: 1];

TSAPDTRPAPGSTAPPAHGV [SEQ ID NO: 5]; or

TSAPDT(Tn)RPAPGSTAPPAHGV [SEQ ID NO: 6].

10. The composition of claim 9 , wherein the threonine in the sequence GST or PDT is synthetically modified to incorporate α-GalNAc-O-Thr (Tn) TACA.

11. A composition, comprising:

an antigen composition comprising a first lipid moiety, a first linker moiety, and an antigen moiety;

a xenoantigen composition comprising a second lipid moiety, a second linker moiety, and a xenoantigen moiety; and

at least one liposomal formulation, wherein the antigen composition and the xenoantigen composition are embedded in the liposomal formulation;

wherein the antigen composition consists essentially of compound 21:

12. A composition comprising:

an antigen composition comprising a first lipid moiety, a first linker moiety, and an antigen moiety, wherein the antigen composition comprises a Pam 3 Cys-MUC1 VNTR-TACA conjugate;

a xenoantigen composition comprising a second lipid moiety, a second linker moiety, and a xenoantigen moiety, wherein the second linker moiety comprises a tetraethyleneglycol (TEG) portion and the xenoantigen moiety comprises α- or β-linked L-rhamnose; and

at least one liposomal formulation, wherein the antigen composition and the xenoantigen composition are embedded in the liposomal formulation.