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Peptide-Based Vaccination and Induction of CD8+ T-Cell Responses Against Tumor Antigens in Breast Cancer

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Abstract

Tumor-associated antigens (TAAs) have been identified in many malignant tumors. Within these TAAs are peptide sequences that bind major histocompatibility complex (MHC) class I and class II molecules recognized by T cells triggering antigen-specific CD8+ cytotoxic T-cell and CD4+ T-helper cell responses. Efforts to develop vaccines for breast cancer have been underway for more than 20 years, including peptide and whole inactivated tumor cell vaccines as well as antigen-loaded dendritic cell vaccines. The majority of vaccine trials have used peptides, including single-peptide and multiple-peptide formulations using either MHC class I and class II epitopes in oil-based emulsions alone or in combination with an adjuvant, such as granulocyte-macrophage colony-stimulating factor, and Toll-like receptor agonists. Preclinical research in vitro and in animal models has been aimed at improving vaccine efficacy by identifying more immunogenic peptides and combinations of peptides and adjuvants and cytokine adjuvants that induce stronger immune responses and prolong T-cell memory. Clinical studies investigating the therapeutic potential of active immunization using peptide vaccines has found no serious side effects. In this review, we examine TAA peptide-based vaccination regimens showing promise in breast cancer patients that are also being investigated in clinical trials of safety and efficacy. We also discuss the current limitations in the peptide vaccination field and areas for future development.

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Abbreviations

APCs:

Antigen-presenting cells

CEA:

Carcinoembryonic antigen

CTLs:

Cytotoxic T lymphocytes

DCs:

Dendritic cells

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HLA:

Human leukocyte antigen

hTERT:

Human telomerase reverse transcriptase

IFN-γ:

Gamma interferon

KLH:

Keyhole limpet hemocyanin

MHC:

Major histocompatibility complex

TAAs:

Tumor-associated antigens

TLRs:

Toll-like receptors

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Acknowledgements

We thank Dr. Naoto Ueno (Department of Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA) for critical reading of the manuscript and comments. This study was supported by a 2011 My Oncology Dream Award to Michiko Harao supported by the Japanese Cancer Society and the University of Texas, MD Anderson Global Academic Program.

Conflict of interest

The authors have no conflicts of interest regarding the subject matter of this review.

Author Contributions

Conception and design: MH, EM, LR. Manuscript writing: MH, LR. Responsible for overall content: MH and LR.

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Authors and Affiliations

  1. Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Michiko Harao & Laszlo G. Radvanyi

  2. Department of Breast Surgical Oncology, Tochigi Cancer Center, Utsunomiya, Japan

    Michiko Harao

  3. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Elizabeth A. Mittendorf

  4. Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL, 33612, USA

    Laszlo G. Radvanyi

  5. Lion Biotechnologies, Woodland Hills, CA, 91367, USA

    Laszlo G. Radvanyi

  6. Lion Biotechnologies, USF Connect, 3802 Spectrum Blvd., Tampa, FL, 33612, USA

    Laszlo G. Radvanyi

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  1. Michiko Harao
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  2. Elizabeth A. Mittendorf
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  3. Laszlo G. Radvanyi
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Correspondence to Laszlo G. Radvanyi.

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Harao, M., Mittendorf, E.A. & Radvanyi, L.G. Peptide-Based Vaccination and Induction of CD8+ T-Cell Responses Against Tumor Antigens in Breast Cancer. BioDrugs 29, 15–30 (2015). https://doi.org/10.1007/s40259-014-0114-1

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