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Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo

  • Authors:
    • Magdalena Gabrysiak
    • Malgorzata Wachowska
    • Joanna Barankiewicz
    • Zofia Pilch
    • Anna Ratajska
    • Ewa Skrzypek
    • Magdalena Winiarska
    • Antoni Domagala
    • Tomasz P. Rygiel
    • Alicja Jozkowicz
    • Louis Boon
    • Jakub Golab
    • Malgorzata Firczuk
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland, Department of Pathology, Center of Biostructure Research, Medical University of Warsaw, 02-004 Warsaw, Poland, Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kracow, Poland, EPIRUS Biopharmaceuticals Netherlands BV, 3584 CM Utrecht, The Netherlands
    Copyright: © Gabrysiak et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3151-3158
    |
    Published online on: April 1, 2016
       https://doi.org/10.3892/or.2016.4723
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Abstract

Photodynamic therapy (PDT) exerts direct cytotoxic effects on tumor cells, destroys tumor blood and lymphatic vessels and induces local inflammation. Although PDT triggers the release of immunogenic antigens from tumor cells, the degree of immune stimulation is regimen-dependent. The highest immunogenicity is achieved at sub-lethal doses, which at the same time trigger cytoprotective responses, that include increased expression of glucose-regulated protein 78 (GRP78). To mitigate the cytoprotective effects of GRP78 and preserve the immunoregulatory activity of PDT, we investigated the in vivo efficacy of PDT in combination with EGF-SubA cytotoxin that was shown to potentiate in vitro PDT cytotoxicity by inactivating GRP78. Treatment of immunocompetent BALB/c mice with EGF-SubA improved the efficacy of PDT but only when mice were treated with a dose of EGF-SubA that exerted less pronounced effects on the number of T and B lymphocytes as well as dendritic cells in mouse spleens. The observed antitumor effects were critically dependent on CD8+ T cells and were completely abrogated in immunodeficient SCID mice. All these results suggest that GRP78 targeting improves in vivo PDT efficacy provided intact T-cell immune system.
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Copy and paste a formatted citation
Spandidos Publications style
Gabrysiak M, Wachowska M, Barankiewicz J, Pilch Z, Ratajska A, Skrzypek E, Winiarska M, Domagala A, Rygiel TP, Jozkowicz A, Jozkowicz A, et al: Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo. Oncol Rep 35: 3151-3158, 2016.
APA
Gabrysiak, M., Wachowska, M., Barankiewicz, J., Pilch, Z., Ratajska, A., Skrzypek, E. ... Firczuk, M. (2016). Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo. Oncology Reports, 35, 3151-3158. https://doi.org/10.3892/or.2016.4723
MLA
Gabrysiak, M., Wachowska, M., Barankiewicz, J., Pilch, Z., Ratajska, A., Skrzypek, E., Winiarska, M., Domagala, A., Rygiel, T. P., Jozkowicz, A., Boon, L., Golab, J., Firczuk, M."Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo". Oncology Reports 35.6 (2016): 3151-3158.
Chicago
Gabrysiak, M., Wachowska, M., Barankiewicz, J., Pilch, Z., Ratajska, A., Skrzypek, E., Winiarska, M., Domagala, A., Rygiel, T. P., Jozkowicz, A., Boon, L., Golab, J., Firczuk, M."Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo". Oncology Reports 35, no. 6 (2016): 3151-3158. https://doi.org/10.3892/or.2016.4723
Copy and paste a formatted citation
x
Spandidos Publications style
Gabrysiak M, Wachowska M, Barankiewicz J, Pilch Z, Ratajska A, Skrzypek E, Winiarska M, Domagala A, Rygiel TP, Jozkowicz A, Jozkowicz A, et al: Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo. Oncol Rep 35: 3151-3158, 2016.
APA
Gabrysiak, M., Wachowska, M., Barankiewicz, J., Pilch, Z., Ratajska, A., Skrzypek, E. ... Firczuk, M. (2016). Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo. Oncology Reports, 35, 3151-3158. https://doi.org/10.3892/or.2016.4723
MLA
Gabrysiak, M., Wachowska, M., Barankiewicz, J., Pilch, Z., Ratajska, A., Skrzypek, E., Winiarska, M., Domagala, A., Rygiel, T. P., Jozkowicz, A., Boon, L., Golab, J., Firczuk, M."Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo". Oncology Reports 35.6 (2016): 3151-3158.
Chicago
Gabrysiak, M., Wachowska, M., Barankiewicz, J., Pilch, Z., Ratajska, A., Skrzypek, E., Winiarska, M., Domagala, A., Rygiel, T. P., Jozkowicz, A., Boon, L., Golab, J., Firczuk, M."Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo". Oncology Reports 35, no. 6 (2016): 3151-3158. https://doi.org/10.3892/or.2016.4723
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