Literature DB >> 20845479

Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

Jarrod P Holmes1, Guy T Clifton, Ritesh Patil, Linda C Benavides, Jeremy D Gates, Alexander Stojadinovic, Elizabeth A Mittendorf, Sathibalan Ponniah, George E Peoples.   

Abstract

BACKGROUND: The authors are conducting clinical trials of the HER-2/neu E75-peptide vaccine in clinically disease-free breast cancer (BC) patients. Their phase 1-2 trials revealed that the E75 + granulocyte-macrophage colony-stimulating factor (GM-CSF) vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8(+) T cells. They assessed the need for and response to a booster after completion of primary vaccination series.
METHODS: BC patients enrolled in the E75 vaccine trials who were ≥6 months from completion of their primary vaccination series were offered boosters with E75 + GM-CSF. Patients were monitored for toxicity. E75-specific CD8(+) T cells were quantified using the human leukocyte antigen-A2:immunoglobulin G dimer before and after boosting.
RESULTS: Fifty-three patients received the vaccine booster. Median time from primary vaccination series was 9 months (range, 6-35 months), and median residual E75-specific immunity was 0.70% (range, 0-3.49%) CD8(+) lymphocytes. Elevated residual immunity (ERI) (CD8(+) E75-specific T cells >0.5%) was seen in 94.4% of patients at 6 months from primary vaccination series versus 48% of patients at >6 months (P = .002). The booster was well tolerated, with only grade 1 and 2 toxicity observed. Local reactions were more robust in patients receiving the booster at 6 months from primary vaccination series compared with those at >6 months (99.4 ± 6.1 mm vs 81.8 ± 4.1 mm, P = .01). In patients lacking ERI, 85% had increased ERI after vaccination (P = .0014).
CONCLUSIONS: The HER-2/neu E75 peptide vaccine E75 stimulates specific immunity in disease-free BC patients. However, immunity wanes with time. A vaccine booster is safe and effective in stimulating E75-specific immunity in those patients without ERI. These results suggest that the booster may be most effective at 6 months after completion of the primary vaccination series. Published 2010 American Cancer Society.

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Year:  2010        PMID: 20845479     DOI: 10.1002/cncr.25586

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  15 in total

1.  Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

Authors:  Elizabeth A Mittendorf; Guy T Clifton; Jarrod P Holmes; Kevin S Clive; Ritesh Patil; Linda C Benavides; Jeremy D Gates; Alan K Sears; Alexander Stojadinovic; Sathibalan Ponniah; George E Peoples
Journal:  Cancer       Date:  2011-10-11       Impact factor: 6.860

2.  Breast Cancer Immunotherapy.

Authors:  Erika Schneble; Dan-Corneliu Jinga; George Peoples
Journal:  Maedica (Buchar)       Date:  2015-06

3.  Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and an attenuated version, E39': An analysis of safety and immune response.

Authors:  Timothy J Vreeland; Jennifer K Litton; Na Qiao; Anne V Philips; Gheath Alatrash; Diane F Hale; Doreen O Jackson; Kaitlin M Peace; Julia M Greene; John S Berry; Guy T Clifton; George E Peoples; Elizabeth A Mittendorf
Journal:  Clin Immunol       Date:  2018-03-21       Impact factor: 3.969

Review 4.  Clinical Development of the E75 Vaccine in Breast Cancer.

Authors:  Guy T Clifton; Victor Gall; George E Peoples; Elizabeth A Mittendorf
Journal:  Breast Care (Basel)       Date:  2016-04-26       Impact factor: 2.860

5.  Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients.

Authors:  E A Mittendorf; G T Clifton; J P Holmes; E Schneble; D van Echo; S Ponniah; G E Peoples
Journal:  Ann Oncol       Date:  2014-06-06       Impact factor: 32.976

Review 6.  Peptides for Vaccine Development.

Authors:  Ian W Hamley
Journal:  ACS Appl Bio Mater       Date:  2022-02-23

Review 7.  Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade.

Authors:  Leisha A Emens
Journal:  Expert Rev Anticancer Ther       Date:  2012-12       Impact factor: 4.512

8.  Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine.

Authors:  Keith L Knutson; Matthew S Block; Nadine Norton; Courtney L Erskine; Timothy J Hobday; Allan B Dietz; Douglas Padley; Michael P Gustafson; Danell Puglisi-Knutson; Toni Kay Mangskau; Saranya Chumsri; Amylou C Dueck; Lavakumar Karyampudi; Glynn Wilson; Amy C Degnim
Journal:  Clin Cancer Res       Date:  2019-11-22       Impact factor: 12.531

9.  The development and use of the E75 (HER2 369-377) peptide vaccine.

Authors:  Guy T Clifton; George E Peoples; Elizabeth A Mittendorf
Journal:  Future Oncol       Date:  2016-04-05       Impact factor: 3.404

10.  Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence.

Authors:  Elizabeth A Mittendorf; Alexandros Ardavanis; Jennifer K Litton; Nathan M Shumway; Diane F Hale; James L Murray; Sonia A Perez; Sathibalan Ponniah; Constantin N Baxevanis; Michael Papamichail; George E Peoples
Journal:  Oncotarget       Date:  2016-10-04
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