Tumor cells from immune privileged sites as base cells for cell-based cancer vaccines

1. A tumor cell-based vaccine for a recipient comprising:

primary immune-privilege tumor cells that constitutively express MHC class I molecules and do not constitutively express MHC class II molecules, wherein the primary immune-privilege tumor cells are genetically modified to express at least one costimulatory molecule, that activates CD4+ T cells, and at least one MHC class II allele, and wherein the MHC class II allele is syngeneic to the recipient, wherein the primary immune-privilege tumor cells are primary ocular melanoma cells.

2. The tumor cell based vaccine according to claim 1 , wherein the primary immune-privilege tumor cells do not express Ii.

3. The tumor cell based vaccine according to claim 2 , wherein the primary tumor cells are genetically modified by introducing a vector comprising nucleotide sequences encoding for the costimulatory molecule and the at least one MHC class II allele protein.

4. The tumor cell base vaccine according to claim 1 , wherein the vaccine comprises at least two different MHC II alleles of the recipient being treated.

5. The tumor cell base vaccine according to claim 3 , wherein the costimulatory molecule is CD80.

6. The tumor cell base vaccine according to claim 3 , wherein the vector is a recombinant retrovirus.

7. The tumor cell base vaccine according to claim 6 , wherein the recombinant retrovirus comprises nucleic acid comprising DNA encoding: (a) at least one MHC class II α chain protein; and (b) at least one MHC class II β chain protein.

8. A method of generating a MHC-II matched allogeneic cell based vaccine that cross reacts with multiple patients and treat metastatic tumors, the method comprising:

providing primary uveal melanoma cells that arise from ocular immune-privileged tissue;

determining the HLA-DR type of the primary uveal melanoma cells;

isolating primary uveal melanoma cells that cannot be induced to express MHC II or Ii;

transducing the isolated primary uveal melanoma cells with at least one vector comprising nucleic acid encoding for the determined HLA-DR allele or a variant thereof and a co stimulatory molecule or variant thereof to provide modified cells that express the transduced HLA-DR and co stimulatory sequences.

9. The method according to claim 8 , wherein the MHC-II matched allogeneic cell based vaccine comprises at least two different MHC II alleles of the subject being treated.

10. The method according to claim 8 , wherein the HLA-DR type is HLA-DR1.

11. The method according to claim 8 , further determining the HLA-A, B of C type of the primary uveal melanoma cells.

12. The method according to claim 9 , wherein vector is a recombinant retrovirus.

13. The method according to claim 12 , wherein the recombinant retrovirus comprises nucleic acid comprising DNA encoding: (a) at least one MHC class II α chain protein; and (b) at least one MHC class II β chain protein.

14. An ex vivo method for inducing an increased population of CD4 + T cells in a subject, comprising:

(a) removing a blood sample from the subject and isolating T-cells;

(b) determining HLA genotypes of the subject;

(c) contacting the isolated T-cells with a vaccine comprising:

a primary ocular melanoma cell that constitutively express MHC class I molecules and does not constitutively express MHC class II molecules and Ii; and is genetically modified to express a co-stimulatory molecule that activates CD4+ T-cells and at least one MHC class II allele, wherein the MHC class II allele is syngeneic to the HLA genotype of the subject; and

(d) reintroducing the activated T-cells into the subject.