Purpose: E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients. Experimental Design: E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented. Results: One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted. Conclusions: E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.Breast cancer is the most common cancer diagnosis in women and the second leading cause of cancer-related death among women.7 Despite advances in standard treatment, a significant proportion of breast cancer patients will ultimately die from recurrent disease, especially aggressive subsets, such as those overexpressing HER2/neu. HER2/neu is a protooncogene expressed in many epithelial malignancies (1). Overexpression of HER2/neu is found in 20% to 25% of breast cancer and confers a poor prognosis (2).Novel approaches are needed to further improve outcomes among breast cancer patients, and one such approach is immunotherapy. Trastuzumab is a monoclonal antibody that targets the HER2/neu protein and is an effective treatment of metastatic breast cancer (3). Several recent large trials have shown that adjuvant trastuzumab decreases recurrence rates compared with chemotherapy alone (4 -6).Another mode of immunotherapy in treating cancer is vaccines. Tumor-associated antigens are proteins expressed by 7 Ries LAG, Harkins D, Krapcho M, et al. (eds.).

Simian immunodeficiency virus (SIV) infection of newborn macaques is a useful animal model to explore novel strategies to reduce perinatal human immunodeficiency virus (HIV) infection. The availability of two easily distinguishable virus isolates, SIVmac251 and the simian/human immunodeficiency virus chimera SHIV-SF33, allows tracing the source of infection following inoculation with both viruses by different routes. In the present study, we evaluated the efficacy of pre- and postinoculation treatment regimens with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) to protect newborn macaques against simultaneous oral SIVmac251 and intravenous SHIV-SF33 inoculation. Untreated newborns became persistently infected following virus inoculation. When three pregnant macaques were given a single subcutaneous dose of PMPA 2 hr before cesarean section, their newborns became SIV-infected following SIV and SHIV inoculation shortly after birth. In contrast, when four newborn macaques were inoculated simultaneously with SIV and SHIV, and started immediately on PMPA treatment for 2 weeks, only one animal became persistently SIV-infected; the remaining three PMPA-treated newborns, however, had some evidence of an initial transient virus infection but were seronegative and healthy at 8 months of age. Our data demonstrate that PMPA treatment can reduce perinatal SIV infection and suggest that similar strategies may also be effective against HIV.

We used the Luminex assay to compare serum cytokine profiles of breast cancer patients (BCa) to healthy controls, node-positive (NP) patients to node-negative (NN), and pre-and post-vaccination serum of BCa vaccinated with a HER2/neu E75 peptide vaccine. Sera from 36 pre-and postvaccination BCa, (12 NP and 24 NN) and 13 healthy, female donors, were evaluated using Luminex technology. Levels of 22 cytokines consisting of interleukin (IL)