Cancer vaccines and vaccination methods
Compositions of multipeptide vaccines comprising at least seven tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from at least seven tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating gynecological and peritoneal cancers using such vaccines.
1. A composition comprising a pharmaceutically acceptable carrier, an adjuvant, and a mixture of at least one major histocompatibility complex (MHC) class I peptide epitope of 8-10 amino acids in length derived from a mesothelin antigen variant having an amino acid sequence selected from the group consisting of: SEQ ID NOs: 19-25 and at least one MHC class I peptide epitope of 8-10 amino acids in length derived from each of at least six different antigens or variants thereof selected from the group consisting of:
a mesothelin antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs: 15-18;
an NY-ESO-1 antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NO: 26 and SEQ ID NO: 27;
an FBP antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NO: 28 and SEQ ID NO: 29;
a HER-2/neu antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs: 30-48;
an IL-13 receptor α2 antigen, wherein the MHC class I peptide epitope has an amino acid sequence of SEQ ID NO: 49;
a MAGE-A1 antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs: 50-55;
an EphA2 antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs: 56-68;
a p53 antigen or variant thereof, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs:69-80;
a k-Ras antigen or variant thereof, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs:81-86;
an Ep-CAM antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs:87-91;
a MUC1 antigen or variant thereof, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NO:92 and SEQ ID NO:93;
a survivin antigen or variant thereof, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs:94-98;
an hTERT antigen or variant thereof, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs:99-104; and
a WT1 antigen, wherein the MHC class I peptide epitope has an amino acid sequence selected from the group consisting of SEQ ID NOs: 105-109.
2. The composition of claim 1 , wherein the composition comprises at least one MHC class I peptide epitope of 8-10 amino acids in length derived from a mesothelin antigen, an NY-ESO-1 antigen, an FBP antigen, a HER-2/neu antigen, an IL-13 receptor α2 antigen, a MAGE-A1 antigen, and an EphA2 antigen.
3. The composition of claim 1 , wherein said composition comprises:
the MHC class I peptide epitope derived from an NY-ESO-1 antigen having the amino acid sequence of SEQ ID NO: 26;
the MHC class I peptide epitope derived from an FBP antigen having the amino acid sequence of SEQ ID NO: 28;
the MHC class I peptide epitope derived from a HER-2/neu antigen having the amino acid sequence of SEQ ID NO: 40;
the MHC class I peptide epitope derived from a IL-13 receptor α2 antigen having the amino acid sequence of SEQ ID NO: 49;
the MHC class I peptide epitope derived from a MAGE-A1 antigen having the amino acid sequence of SEQ ID NO: 55; and
the MHC class I peptide epitope derived from an EphA2 antigen having the amino acid sequence of SEQ ID NO: 66.
4. The composition of claim 1 , wherein the composition further comprises any one or more of dextrose, dimethyl sulphoxide (DMSO), and dextran.
5. The composition of claim 1 , wherein each of the MHC class I peptide epitopes is present in the composition at a concentration between about 10 μg/ml and about 20 μg/ml.
6. The composition of claim 1 , wherein each of the MHC class I peptide epitopes is present in the composition at a concentration of 20 μg/ml.
7. The composition of claim 1 , wherein each of the MHC class I peptide epitopes is present in the composition at a concentration of 2 μg/ml.
8. The composition of claim 1 , wherein each of the MHC class I peptide epitopes is pegylated.