Vaccine for the prevention of breast cancer relapse
View Patent ↗The invention features methods to induce and maintain a protective cytotoxic T-lymphocyte response to a peptide of the HER2/neu oncogene, E75, with the effect of inducing and maintaining protective or therapeutic immunity against breast cancer in a patient in clinical remission. The methods comprise administering to the patient an effective amount of a vaccine composition comprising a pharmaceutically acceptable carrier, an adjuvant such as recombinant human GM-CSF, and the E75 peptide at an optimized dose and schedule. The methods further comprise administering an annual or semi-annual booster vaccine dose due to declining E75-specific T cell immunity. The invention also features vaccine compositions for use in the methods.
1. A method of inducing protective or therapeutic immunity against breast cancer recurrence in a subject having an immunohistochemistry (IHC) rating of 1 + or 2 + for HER2/neu protein expression and a fluorescence in situ hybridization (FISH) rating of less than about 2.0 for HER2/neu gene expression, said method comprising administering to the subject an effective amount of a composition comprising a pharmaceutically effective carrier and a peptide having the amino acid sequence SEQ ID NO:2.
2. The method of claim 1 wherein the composition is administered by injection or inoculation.
3. The method of claim 2 , wherein the injection is an intradermal injection.
4. The method of claim 2 , wherein the composition is injected in one or more split doses.
5. The method of claim 4 , wherein the doses contain an optimized amount of the peptide.
6. The method of claim 4 , wherein the injection sites are located about 5 cm apart from each other.
7. The method of claim 1 , wherein the composition is administered six times over 6 months until the protective immunity is established.
8. The method of claim 1 , further comprising administering to the subject a booster after the primary immunization schedule is completed, the booster comprising an effective amount of a vaccine booster composition comprising a pharmaceutically effective carrier and a peptide having SEQ ID NO:2.
9. The method of claim 8 wherein the booster composition is administered by injection.
10. The method of claim 9 , wherein the injection is an intradermal injection.
11. The method of claim 8 , wherein the booster composition is injected in one or more separate doses.
12. The method of claim 11 , wherein two doses contain equal concentrations of the peptide.
13. The method of claim 11 , wherein the injection sites are located about 5 cm apart from each other.
14. The method of claim 8 , wherein the booster is administered about every six or more months after the primary immunization schedule is completed.
15. The method of claim 1 , wherein the subject is a human.
16. The method of claim 15 , wherein the human expresses human leukocyte antigen A2.
17. The method of claim 15 , wherein the human expresses human leukocyte antigen A3.
18. The method of claim 1 , wherein the subject is in complete clinical remission after diagnosis of node positive or node negative breast cancer.
19. The method of claim 1 , wherein the subject is in partial clinical remission for breast cancer.
20. The method of claim 1 , wherein the composition further comprises an adjuvant.
21. The method of claim 20 , wherein the adjuvant is recombinant human granulocyte macrophage-colony stimulating factor.
22. The method of claim 8 , wherein the vaccine booster composition further comprises an adjuvant.
23. The method of claim 22 , wherein the adjuvant is recombinant human granulocyte macrophage-colony stimulating factor.
24. The method of claim 1 , wherein administering the composition induces a cytotoxic T lymphocyte response to the peptide having the amino acid sequence SEQ ID NO:2.
25. The method of claim 15 , wherein the human had node positive breast cancer.
26. The method of claim 15 , wherein the human had node negative breast cancer.
27. The method of claim 1 , wherein the composition comprises 1 mg of the peptide and between about 0.01 to 0.5 mg of human granulocyte macrophage-colony stimulating factor as an adjuvant.
28. The method of claim 1 , wherein the composition comprises 1 mg of the peptide and about 0.25 mg of human granulocyte macrophage-colony stimulating factor as an adjuvant.
29. The method of claim 1 , wherein the composition is administered at least three to six times on a monthly basis.
30. The method of claim 7 , wherein protective immunity is established by an statistically significant increase in the presence of CD8 + cells specific for the peptide in peripheral blood mononuclear cells of the subject when compared to pre-vaccine levels.
31. The method of claim 8 , wherein the booster is administered every six months after the primary immunization schedule is completed.
32. A method of inducing protective or therapeutic immunity against breast cancer recurrence in a human subject having an immunohistochemistry (IHC) rating of 1 + or 2 + for HER2/neu protein expression and a fluorescence in situ hybridization (FISH) rating of less than about 2.0 for HER2/neu gene expression, said method comprising,
(a) monthly administration of a vaccine composition to the subject for at least three to six months, the vaccine composition comprising a pharmaceutically effective carrier, about 1 mg of a peptide having the amino acid sequence SEQ ID NO:2, and about 0.125 to 0.250 mg of human granulocyte-macrophage colony stimulating factor; and
(b) administration of a vaccine booster composition to the subject 6 or 12 months after the primary immunization schedule is completed, the vaccine booster composition comprising a pharmaceutically effective carrier, about 1 mg of a peptide having the amino acid sequence SEQ ID NO:2, and about 0.125 to 0.250mg of human granulocyte-macrophage colony stimulating factor.
33. The method of claim 32 , wherein the vaccine composition and the booster composition are administered by injection or inoculation.
34. The method of claim 33 , wherein the vaccine composition is administered by intradermal injection.
35. The method of claim 33 , wherein the booster composition is administered by intradermal injection.
36. The method of claim 32 , wherein the vaccine composition and the vaccine booster composition are administered in one or more split doses located about 5 cm apart.
37. The method of claim 32 , wherein the human subject expresses human leukocyte antigen A2 or A3.
38. The method of claim 1 , wherein the subject has an IHC rating of 1+ for HER2/neu protein expression.
39. The method of claim 32 , wherein the subject has an IHC rating of 1+ for HER2/neu protein expression.