Vaccine for the prevention of the recurrence HER2/neu expressing cancer
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 recurrence of a HER2/neu expressing tumor in a subject, wherein the tumor is characterized as having 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. A method of inducing protective or therapeutic immunity against breast cancer recurrence in a subject having an 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.
3. A method of inducing protective or therapeutic immunity against recurrence of HER2/neu expressing tumor in a subject, wherein the tumor is characterized as 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 or a variant thereof, wherein immunity is established by a 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.
4. The method of claim 1 , wherein the composition is administered by injection or inoculation.
5. The method of claim 4 , wherein the injection is an intradermal injection.
6. The method of claim 5 , wherein the composition is injected in one or more split doses.
7. The method of claim 6 , wherein the injection sites are located about 5 cm apart from each other.
8. The method of claim 1 , wherein the composition is administered at least three to six times on a monthly basis until the protective immunity is established.
9. 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, or variant thereof.
10. The method of claim 9 , wherein the booster composition is administered by injection.
11. The method of claim 10 , wherein the injection is an intradermal injection.
12. The method of claim 10 , wherein the booster composition is injected in one or more separate doses.
13. The method of claim 12 , wherein the injection sites are located about 5 cm apart from each other.
14. The method of claim 9 , 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 composition further comprises an adjuvant.
19. The method of claim 18 , wherein the adjuvant is recombinant human granulocyte macrophage-colony stimulating factor.
20. The method of claim 9 , wherein the vaccine booster 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 1 , wherein the composition comprises 1mg of the peptide and between about 0.01 to 0.5 mg of human granulocyte macrophage-colony stimulating factor as an adjuvant.
23. The method of claim 1 , wherein the composition comprises 1mg of the peptide and about 0.25 mg of human granulocyte macrophage-colony stimulating factor as an adjuvant.