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Induction of an antitumor response using dendritic cells transfected with DNA constructs encoding the HLA-A*02:01-restricted epitopes of tumor-associated antigens in culture of mononuclear cells of breast cancer patients

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Abstract

Advances in oncoimmunology related to the definition of the basic mechanisms of the formation of antitumor immune response, as well as the opening of tumor-associated antigens recognized by immune cells, allowed to start developing ways to influence the effector cells of the immune system to generate effective antitumor cytotoxic response. We investigated the possibility to stimulate an antitumor response in a culture of mononuclear cells of breast cancer patients by dendritic cells transfected with HLA-A*02:01-restricted DNA constructs. We isolated dendritic cells from peripheral blood monocytes and delivered our constructs to these cells by magnetic transfection. Additionally, a series of experiments with loading of dendritic cells with autologous tumor cell lysate antigens was conducted. We have shown that dendritic cells transfected with the HLA-A*02:01-restricted DNA constructs are effective in inducing an antitumor response in a culture of mononuclear cells of breast cancer patients. Dendritic cells transfected with DNA constructor dendritic cells loaded with lysate antigens revealed a comparable stimulated cytotoxic response of mononuclear cells to these two ways of antigen delivery. We conclude that using DNA constructs in conjunction with patient stratification by HLA type allows the application of transfected DCs as an effective method to stimulate antitumor immunity in vitro.

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Abbreviations

DC:

Dendritic cells

MNC:

Mononuclear cells

TC:

Tumor cells

LDH:

Lactate dehydrogenase

TAAs:

Tumor-associated antigens

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Acknowledgments

This work was supported by the Federal target program “Research and development in priority areas of scientific and technological complex development of Russia for 2014-2020” (Agreement No 14.607.21.0043. The unique identifier for Applied Scientific Research RFMEFI60714X0043). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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Authors and Affiliations

  1. Department of Molecular Immunology, Federal State Budgetary Institution “Research Institute of Fundamental and Clinical Immunology”, Yadrintsevskaya St. 14, Novosibirsk, Novosibirsk, Russia, 630099

    Sergey Vital’evich Sennikov, Julia Alexandrovna Shevchenko, Vasilii Vasil’evich Kurilin, Julia Nikolaevna Khantakova, Julia Anatol’evna Lopatnikova & Alexander Alexandrovich Khristin

  2. 3rd Oncological Department, City Clinical Hospital #1, Zalessky St. 6, Siberian Field, Novosibirsk, Russia, 630047

    Sergey Vasil’evich Sidorov

  3. Vaccine Department, Avaxis Biotherapeutics LLC, Technopark St. 1 116, Koltsovo, Novosibirsk Region, Russia, 630559

    Elena Vasil’evna Gavrilova, Rinat Amirovich Maksyutov & Amir Zakievich Maksyutov

  4. Novosibirsk State University, Pirogova-90 St. 1, Novosibirsk, Russia

    Anastasiya Yur’evna Bakulina

Authors
  1. Sergey Vital’evich Sennikov
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  2. Julia Alexandrovna Shevchenko
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  11. Amir Zakievich Maksyutov
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Correspondence to Sergey Vital’evich Sennikov.

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The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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Sennikov, S.V., Shevchenko, J.A., Kurilin, V.V. et al. Induction of an antitumor response using dendritic cells transfected with DNA constructs encoding the HLA-A*02:01-restricted epitopes of tumor-associated antigens in culture of mononuclear cells of breast cancer patients. Immunol Res 64, 171–180 (2016). https://doi.org/10.1007/s12026-015-8735-0

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