Safety and Efficacy Study of HER2/Neu (E75) Vaccine in Breast Cancer

The objectives of this study are the following: 1. To assess safety and document local and systemic toxicity to the peptide vaccine (E75) in node-negative breast cancer patients. 2. To determine the optimal dose of the immunoadjuvant, GM-CSF, necessary to elicit an in vivo cellular immune response to the peptide vaccine yet limit toxicity. 3. To determine the optimal inoculation schedule to elicit an in vivo cellular immune response to the peptide vaccine. 4. To correlate the efficiency of eliciting an in vivo cellular immune response to the peptide vaccine with the degree of HER2/neu expression in the patient's tumor.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Breast cancer and negative lymph nodes
2. HLA-A2+ and/or HLA-A3+ to receive the vaccine. HLA-A2-, HLA-A3- patients will be eligible to be included in the control group.
3. Immunologically intact with a good performance status (defined below).
4. Without evidence of disease.
5. Patients may enroll while receiving appropriate hormonal therapy for their disease.
6. Completion of all standard first-line therapies (but may still be on hormonal therapy)

Exclusion Criteria:

1. HLA-A2- and/or HLA-A3- patients will not be vaccinated
2. Anergic by the Mantoux panel of recall antigens
3. Receiving immunosuppressive therapy
4. In poor health (Karnofsky \<60%, ECOG \>2)
5. Tbili \>1.5 mg/dL and creatinine\>2 mg/dL
6. Pregnancy (urine HCG)
7. Active metastatic disease
8. Involved in other experimental protocols (unless approval is first obtained by the other study PI)
9. Refusal of standard therapies

• BACKGROUNDMittendorf EA, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer. Ann Surg Oncol. 2006 Aug;13(8):1085-98. doi: 10.1245/ASO.2006.03.069. Epub 2006 Jul 24. PMID 16865596
• BACKGROUNDDehqanzada ZA, Storrer CE, Hueman MT, Foley RJ, Harris KA, Jama YH, Kao TC, Shriver CD, Ponniah S, Peoples GE. Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients. Clin Cancer Res. 2006 Jan 15;12(2):478-86. doi: 10.1158/1078-0432.CCR-05-1425. PMID 16428490
• BACKGROUNDWoll MM, Fisher CM, Ryan GB, Gurney JM, Storrer CE, Ioannides CG, Shriver CD, Moul JW, McLeod DG, Ponniah S, Peoples GE. Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for monitoring the in vivo immune response to a HER2/neu vaccine in breast and prostate cancer patients. J Clin Immunol. 2004 Jul;24(4):449-61. doi: 10.1023/B:JOCI.0000029117.10791.98. PMID 15163902
• RESULTPeoples GE, Gurney JM, Hueman MT, Woll MM, Ryan GB, Storrer CE, Fisher C, Shriver CD, Ioannides CG, Ponniah S. Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients. J Clin Oncol. 2005 Oct 20;23(30):7536-45. doi: 10.1200/JCO.2005.03.047. Epub 2005 Sep 12. PMID 16157940
• RESULTMittendorf EA, Gurney JM, Storrer CE, Shriver CD, Ponniah S, Peoples GE. Vaccination with a HER2/neu peptide induces intra- and inter-antigenic epitope spreading in patients with early stage breast cancer. Surgery. 2006 Mar;139(3):407-18. doi: 10.1016/j.surg.2005.06.059. PMID 16546506
• RESULTHueman MT, Stojadinovic A, Storrer CE, Dehqanzada ZA, Gurney JM, Shriver CD, Ponniah S, Peoples GE. Analysis of naive and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunol Immunother. 2007 Feb;56(2):135-46. doi: 10.1007/s00262-006-0188-9. Epub 2006 Jun 17.