Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or VSports app下载. mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

Review
. 2008 Oct;57(10):1511-21.
doi: 10.1007/s00262-008-0540-3. Epub 2008 Jun 7.

The E75 HER2/neu peptide vaccine (VSports app下载)

Elizabeth A Mittendorf  1 , Jarrod P Holmes, Sathibalan Ponniah, George E Peoples
Affiliations
Review

The E75 HER2/neu peptide vaccine (V体育ios版)

Elizabeth A Mittendorf (VSports注册入口) et al. Cancer Immunol Immunother. 2008 Oct.

Abstract

E75 (HER2/neu 369-377) is an immunogenic peptide from the HER2/neu protein which is overexpressed in many breast cancer patients. A large amount of preclinical work and a small number of Phase I trials have been completed evaluating the vaccine potential of the E75 peptide mixed with an immunoadjuvant. Our group has performed two concurrent E75 + GM-CSF Phase II trials in node-positive and node-negative disease-free breast cancer patients. These trials, totaling 186 patients, were designed to assess the ability of the E75 vaccine to prevent disease recurrence in these high risk patients. In this review article, we discuss the safety of the vaccine, the immunologic response to the peptide, and most importantly, the potential clinical benefit of the vaccine. The recurrence rate, mortality associated with recurrence, and the distribution of recurrences are presented and discussed. Additionally, the lessons learned from these trials to include optimal dosing and the need for booster inoculations are addressed VSports手机版. We also present data exploring possible explanations and mechanisms behind the potential clinical utility of this simple single epitope vaccine. Finally, we present some of the future directions for our Cancer Vaccine Development Program assessing multi-epitope peptide vaccines and combination immunotherapies. .

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Immune responses after vaccination with E75-peptide. a Delayed type hypersensitivity (DTH) reactions to the E75 peptide were used to assess in vivo immunologic response. Post-vaccination DTH to the E75 peptide was significantly larger (14.0 ± 1.4 mm) then to normal saline control (2.1 ± 0.5 mm); P < 0.0001. b A dimer assay detecting vaccine-induced E75-specific CD8+ cytotoxic T lymphocytes (CTL) was used to assess in vitro immune response. The median levels of E75-specific CTL were significantly increased from pre-vaccination levels (0.39%; range, 0–3.28%) to a maximum level (1.8%; range, 0.4–12.2%; P < 0.0001) and post-vaccination level (0.70%; range, 0.06–2.91%; P = 0.002). There was no difference between pre-vaccine levels and long-term (6 month) levels of E75-specific CTL [27]
Fig. 2
Fig. 2
Recurrence and survival rates for patients completing a HER2/neu (E75) vaccine trial for the prevention of recurrence in high-risk breast cancer patients (n = 177). The control and vaccinated groups had recurrence rates of 14.8 and 8.3%, respectively (P = 0.17), and mortality rates of 6.2 and 1.0%, respectively (P = 0.1). In the recurrent patients, the mortality rate for the control and vaccinated groups were 41.7 and 12.5%, respectively (P = 0.3) [32]
Fig. 3
Fig. 3
Clinical and immunologic data in patients receiving the optimal biologic dose (OBD) versus all others. The optimal dose group (ODG; n = 29) received 1,000 μg E75 + 250 μg for 6 inoculations. The suboptimal dose group (SDG; n = 70) consists of the combined 6 remaining dose groups. a There was no significant difference identified in local (grade 1 and 2, P = 0.58) or systemic toxicity (grade 0, P = 1; grade 1, P = 0.64; grade 2, P = 0.72; grade 3, P = 1). b Orthogonal mean DTH response (mm) between the ODG versus SDG showed no difference to the normal saline control inoculum (3.0 ± 1.1 vs. 2.0 ± 0.5 mm). DTH to the peptide was significantly elevated in the ODG vs. the SDG (21.5 ± 2.5 vs. 11.3 ± 1.3 mm, P = 0.00021). c Dimer assay was used to detect E75-specific CD8+ T-cells. There was a significant difference in the ODG vs. SDG in the average pre-vaccine CD8+ E75-specific T-cell levels (0.91 ± 0.13 vs. 0.54 ± 0.11%, P = 0.03). No significant difference was seen between the average maximum CD8+ E75-specific T-cell levels. The optimal dose showed a trend toward an increase in the average of monthly post-vaccination percent of CD8+ E75-specific T-cells (0.87 ± 0.10 vs. 0.67 ± 0.05%, P = 0.07). No difference was seen in the average long-term CD8+ E75-specific T-cell levels between groups at 6 months. d Compared to the SDG, the ODG demonstrated a trend toward lower recurrence rates (P = 0.27). The ODG consisted of younger patients with more aggressive disease, however, they have significantly shorter median follow-up [33]
Fig. 4
Fig. 4
Location of recurrences in control (C-R) (n = 12) and vaccinated groups (V-R) (n = 8) enrolled in a HER2/neu (E75) breast cancer vaccine trial. No bone-only recurrences were observed in the V-R patients. Asterisks denote statistical significance [32]
Fig. 5
Fig. 5
Correlation between phenotypic (dimer) and functional (cytotoxicity) immunologic responses in node positive breast cancer patients receiving the E75-peptide vaccine. Results depicted are for the first 53 patients enrolled in a clinical trial of the E75 vaccine in node-positive breast cancer patients. a Prevaccination (Pre-Vac) and maximum (Max) responses are given for clonal expansion of E75-specific cytotoxic T lymphocytes. b Functional assessment of short-term cultured, peptide-stimulated peripheral blood mononuclear cells in standard chromium-release assays against a panel of HLA-A2+, HER2/neu + tumor targets with nonspecific lysis of HLA-A2−, HER2/neu + tumor targets subtracted [26]
See this image and copyright information in PMC

References

    1. Boon T, Coulie PG, Van den Eynde B. Tumor antigens recognized by T cells. Immunol Today. 1997;18:267–268. doi: 10.1016/S0167-5699(97)80020-5. - DOI - PubMed
    1. Rosenberg SA. Cancer vaccines based on the identification of genes encoding cancer regression antigens. Immunol Today. 1997;18:175–182. doi: 10.1016/S0167-5699(97)84664-6. - DOI - PubMed
    1. Van den Eynde B, Brichard VG. New tumor antigens recognized by T cells. Curr Opin Immunol. 1995;7:674–681. doi: 10.1016/0952-7915(95)80076-X. - DOI - PubMed
    1. Ko BK, Kawano K, Murray JL, Disis ML, Efferson CL, Kuerer HM, Peoples GE, Ioannides CG. Clinical studies of vaccines targeting breast cancer. Clin Cancer Res. 2003;9:3222–3234. - PubMed
    1. Mittendorf EA, Peoples GE, Singletary SE. Breast cancer vaccines: promise for the future or pipe dream? Cancer. 2007;110:1677–1686. doi: 10.1002/cncr.22978. - DOI - PubMed

Publication types

MeSH terms