A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

Wiedermann, Ursula; Wiltschke, Christoph; Jasińska, Joanna; Kundi, Michael; Zurbriggen, Rinaldo; Garner-Spitzer, Erika; Bartsch, Rupert; Steger, G.; Pehamberger, Hubert; Scheiner, Otto; Zielinski, Christoph

doi:10.1007/s10549-009-0666-9

Cited by 101 publications

(67 citation statements)

References 38 publications

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“…Mostly, their number and function have been investigated in relation to autoimmune diseases, in graftversus-host reactions and in cancer (30,32,33). We have previously demonstrated that FOXP3 + T-regs appear to relatively decrease postbooster in normal responders, which was shown upon hepatitis A vaccination in healthy donors and in breast cancer patients receiving a Her-2/neu vaccine (34). Also, the application of a prostate cancer vaccine resulted in lower T-reg numbers postvaccination in investigated patients; additionally reduced T-reg activity postbooster correlated positively with the overall survival of these patients (35).…”

Section: Discussionmentioning

confidence: 99%

Tick-Borne Encephalitis (TBE) and Hepatitis B Nonresponders Feature Different Immunologic Mechanisms in Response to TBE and Influenza Vaccination with Involvement of Regulatory T and B Cells and IL-10

Garner-Spitzer

Wagner

Paulke‐Korinek

et al. 2013

The Journal of Immunology

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Low responsiveness/nonresponsiveness is characterized by an insufficient immune response upon primary and/or booster vaccination and affects 1–10% of vaccinees. In the current study, we aimed to investigate whether nonresponsiveness is an Ag/vaccine-specific phenomenon and to clarify underlying immunological mechanisms. Nonresponders to tick-borne encephalitis (TBE) or hepatitis B Ag with a history of previous TBE vaccinations were booster vaccinated with TBE and influenza vaccine and compared with TBE high responders in terms of humoral and cellular immune response. Postboosters in TBE high responder existing TBE titers increased, and solid humoral responses to influenza vaccine were induced. In TBE nonresponders, low to undetectable prevaccination TBE titers remained low, whereas sufficient influenza Abs were induced. In both TBE groups, a positive correlation of humoral and cellular immune response was seen as high/low TBE titers were associated with sufficient/lack of Ag-specific T cell proliferation. Furthermore, responses to influenza were robust in terms of Abs and cytokine production. In contrast, in hepatitis B nonresponders, sufficient humoral responses to TBE and influenza Ags were induced despite lacking specific IL-2 and IFN-γ production. Importantly, these patients showed high IL-10 baseline levels in vitro. HLA-DR subtypes associated with hepatitis B nonresponsiveness were overrepresented in this group, and high IL-10 levels were linked to these subtypes. Whereas TBE and hepatitis B nonresponders had increased IL-10–producing FOXP3+ T regulatory cells upon vaccination, only in hepatitis B nonresponders, showing elevated prevaccination IL-10 levels, a prominent population of B regulatory cells was detected. We conclude that immunological pathways of nonresponsiveness follow different patterns depending both on vaccine Ag and genetic predisposition of the vaccinee.

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Section: Discussionmentioning

confidence: 99%

Tick-Borne Encephalitis (TBE) and Hepatitis B Nonresponders Feature Different Immunologic Mechanisms in Response to TBE and Influenza Vaccination with Involvement of Regulatory T and B Cells and IL-10

Garner-Spitzer

Wagner

Paulke‐Korinek

et al. 2013

The Journal of Immunology

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“…Wiedermann and co authors have shown that vaccination with 3 HER-2 peptides representing B-cell epitopes of the extracellular domain of HER-2 induces specific IgG antibodies in mice with strong anti-tumor activity in vitro and in vivo. 31 The virosomal formulated HER-2 multipeptide vaccine was safe, well tolerated and effective in overcoming immunological tolerance resulting in clinical benefit comparable to passive anti-HER-2 antibody therapy. Delivery systems for HER-2 antigen with special focus on T and B cell peptide vaccines for breast cancer improving anti-cancer responses have been reviewed.…”

Section: Unique Peptide B-cell Epitope Vaccinesmentioning

confidence: 99%

A paradigm shift: Cancer therapy with peptide-based B-cell epitopes and peptide immunotherapeutics targeting multiple solid tumor types: Emerging concepts and validation of combination immunotherapy

Kaumaya

2015

Human Vaccines & Immunotherapeutics

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“…Furthermore, a phase I clinical trial, employing anti-Her-2/neu multi-peptide-loaded influenza virosomes, for metastatic breast cancer patients, revealed increased antigen-specific humoral and cellular responses and diminished Treg activity in most of the treated patients. 50 The replication-deficient adenovirus (Ads) has also been widely used as vector for gene delivery in preclinical models and clinical applications, showing its ability to induce strong inflammatory and immune responses. Pentons (Pts), noncovalent complexes located at each of the 12 vertices of the virion, are involved in the virion attachment and entry into the target-cell.…”

Section: In Vitro and In Vivomentioning

confidence: 99%

Modulation of Dendritic Cells by Nanotechnology-Based Immunotherapeutic Strategies

Mogrão¹,

Costa²,

Gaspar³

et al. 2016

j biomed nanotechnol

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In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking immune tolerance. Immunotherapy has been, for the last two decades, an attractive and promising therapeutic approach to fight cancer. This review will approach the nature of the immune response during cancer development and its correlation with DC function, as well as cancer vaccine principles and limitations. An overview of several delivery strategies used for in vivo modulation of DCs and direct activation of T cells will be provided, highlighting their advantages, limitations, and optimization strategies. This manuscript also presents a critical and systematic review of recent clinical trials that are investigating the therapeutic effect of these approaches, discussing prognostic outcomes of combined-treatment modalities.

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A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

Cited by 101 publications

References 38 publications

Tick-Borne Encephalitis (TBE) and Hepatitis B Nonresponders Feature Different Immunologic Mechanisms in Response to TBE and Influenza Vaccination with Involvement of Regulatory T and B Cells and IL-10

Tick-Borne Encephalitis (TBE) and Hepatitis B Nonresponders Feature Different Immunologic Mechanisms in Response to TBE and Influenza Vaccination with Involvement of Regulatory T and B Cells and IL-10

A paradigm shift: Cancer therapy with peptide-based B-cell epitopes and peptide immunotherapeutics targeting multiple solid tumor types: Emerging concepts and validation of combination immunotherapy

Modulation of Dendritic Cells by Nanotechnology-Based Immunotherapeutic Strategies

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