IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0602214
(2008-04-11)
|
등록번호 |
US-8222214
(2012-07-17)
|
국제출원번호 |
PCT/US2008/060044
(2008-04-11)
|
§371/§102 date |
20091130
(20091130)
|
국제공개번호 |
WO2008/150577
(2008-12-11)
|
발명자
/ 주소 |
- Peoples, George E.
- Sathibalan, Ponniah
|
출원인 / 주소 |
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
|
대리인 / 주소 |
Nelson Mullins Riley & Scarborough LLP
|
인용정보 |
피인용 횟수 :
2 인용 특허 :
9 |
초록
▼
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
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.
대표청구항
▼
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,
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.
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