Vaccine in combination with an immune checkpoint inhibitor for use in treating cancer

1. A method of treatment of or vaccination for cancer in a patient, comprising the steps of:

i) inhibiting an immune checkpoint by administering an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is an anti-CTLA-4 antibody and wherein the immune checkpoint inhibitor down-regulates or blocks the immune checkpoint; and

simultaneously, separately or sequentially administering: a cocktail of polypeptides comprising:

a) a polypeptide consisting of a sequence of SEQ ID NO. 1 or a fragment thereof comprising at least 12 amino acids;

b) a polypeptide consisting of a sequence of SEQ ID NO. 2 or a fragment thereof comprising at least 12 amino acids; and

c) a polypeptide consisting of a sequence of SEQ ID NO. 3 or a fragment thereof comprising at least 12 amino acids

wherein the method produces a synergistic effect in the treatment of or vaccination for cancer in the patient.

2. The method according to claim 1 , wherein the synergistic effect comprises an improved clinical outcome in the patient.

3. The method according to claim 2 , wherein the improved clinical outcome is one or more of an improved overall survival and/or an improved effect on tumour size or on the extent of tumour in the body as compared to that obtained with a method in which only an immune checkpoint is inhibited or only the cocktail of polypeptides is administered.

4. The method according to claim 1 , wherein steps i) and ii) are performed within 4 months of each other.

5. The method of treatment according to claim 1 , wherein the anti-CTL 4-4 antibody is selected from the group consisting of ipilimumab and tremelimumab.

6. The method of treatment according to claim 1 , wherein the fragment of SEQ ID NO. 1 comprises at least 14 amino acids, the fragment of SEQ ID NO. 2 comprises at least 14 amino acids and the fragment of SEQ ID NO. 3 comprises at least 14 amino acids.

7. The method of treatment according to claim 6 , wherein the fragment of SEQ ID NO, 1 comprises at least 20 amino acids.

8. The method of treatment according to claim 1 , wherein the cocktail of polypeptides comprises a polypeptide consisting of the sequence of SEQ ID NO. 1, a polypeptide consisting of the sequence of SEQ ID NO. 2 and a polypeptide consisting of the sequence of SEQ ID NO. 3.

9. The method of treatment according to claim 1 , wherein step i) further comprises the step of administering a second immune checkpoint inhibitor, wherein the second immune checkpoint inhibitor is an anti-PD-1 antibody.

10. The method of treatment according to claim 9 , wherein the anti-CTLA-4 antibody is ipilimumab and the anti-PD-1 antibody is nivolumab.

11. The method of treatment according to claim 1 , wherein step i) and/or ii) is performed simultaneously, separately or sequentially with the administration of a further therapeutic ingredient to the patient.

12. The method of treatment according to claim 1 , wherein a polypeptide in the cocktail of polypeptides is linked to a further substance.

13. A method of treatment of or vaccination for cancer in a patient,

comprising the steps of:

i) inhibiting an immune checkpoint by administering an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is an anti-PD-1 antibody and wherein the immune checkpoint inhibitor down-regulates or blocks the immune checkpoint; and

ii) simultaneously, separately or sequentially administering: a cocktail of polypeptides comprising:

a) a polypeptide consisting of a sequence of SEQ ID NO. 1 or a fragment thereof comprising at least 12 amino acids;

b) a polypeptide consisting of a sequence of SEQ ID NO. 2 or a fragment thereof comprising at least 12 amino acids; and

c) a polypeptide consisting of a sequence of SEQ ID NO. 3 or a fragment thereof comprising at least 12 amino acids,

wherein the method produces a synergistic effect in the treatment of or vaccination for cancer in the patient.

14. The method of treatment according to claim 13 , wherein the cocktail of polypeptides comprises a polypeptide consisting of the sequence of SEQ ID NO. 1, a polypeptide consisting of the sequence of SEQ ID NO. 2 and a polypeptide consisting of the sequence of SEQ ID NO. 3.

15. The method of treatment according to claim 13 , wherein the anti-PD-1 antibody is selected from the group consisting of nivolumab and pembrolizumab.

16. The method of treatment according to claim 13 , wherein a polypeptide in the cocktail of polypeptides is linked to a further substance.

17. A method of treatment of or vaccination for cancer in a patient, comprising the steps of:

i) inhibiting an immune checkpoint by administering an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is an anti-PD-L1 antibody and wherein the immune checkpoint inhibitor down-regulates or blocks the immune checkpoint; and

ii) simultaneously, separately or sequentially administering: a cocktail of polypeptides comprising:

a) a polypeptide consisting of a sequence of SEQ ID NO. 1 or a fragment thereof comprising at least 12 amino acids;

b) a polypeptide consisting of a sequence of SEQ ID NO. 2 or a fragment thereof comprising at least 12 amino acids; and

c) a polypeptide consisting of a sequence of SEQ ID NO. 3 or a fragment thereof comprising at least 12 amino acids,

wherein the method produces a synergistic effect in the treatment of or vaccination for cancer in the patient.

18. The method of treatment according to claim 17 , wherein the cocktail of polypeptides comprises a polypeptide consisting of the sequence of SEQ ID NO. 1, a polypeptide consisting of the sequence of SEQ ID NO. 2 and a polypeptide consisting of the sequence of SEQ ID NO. 3.

19. The method of treatment according to claim 17 , wherein the anti-PD-L1 antibody is selected from the group consisting of MPDL3280A, 13BMS-936559 and MEDI4736.

20. The method of treatment according to claim 17 , wherein a polypeptide in the cocktail of polypeptides is linked to a further substance.