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Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma

Received: 26 October 2020    Accepted: 11 November 2020    Published: 4 December 2020
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Abstract

Anticancer xenogeneic vaccine – is an agent, containing antigens of embryonic origin that underwent biotransformation under the action of cytotoxic proteins of В. subtilis B-7025. Anticancer efficacy of the vaccine is implemented by breaking immune system tolerance to own tumor antigens due to the antigenic similarity between tumor and embryonic proteins. The experiments were conducted in Wistar female rats (age 2.5 months and weight 200-220 g, bred at the animal house of R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology). The care and use of the experimental animals have been performed in accordance with generally accepted international rules for conducting experiments in experimental animals. As an experimental tumor model, we have used Walker carcinosarcoma. In preclinical and clinical trials, success has been demonstrated in the use of a combination of anticancer vaccines with chemotherapy to achieve a synergistic effect, even if the dose and schedule of administration of the agents needed to be optimized. It has been shown that some drugs (doxorubicin, cyclophosphamide, docetaxel) induce immunological death of tumor cells, increase the expression of tumor-associated antigens, HLA-peptide complexes, thus sensitizing the tumor in vaccine-induced T-cell killing. It was determined that simultaneous administration of anticancer vaccines (regardless of the antigenic composition) and Doxorubicin resulted in a significant increase of survival and average lifespan of the experimental animals. The treated animals at the end of the experiment presented with increased cytotoxicity of lymphocytes and macrophages (both direct and antibody-dependent), suggesting a reduced level of immunosuppression in experimental animals. In the group of rats, receiving Dox, the serum had no effect on the activity of lymphocytes. These data suggest that during the development of tumor the serum accumulates humoral factors, capable of blocking lymphocyte activity. Yet, as a result of additional activation (due to anticancer vaccines), the conditions are provided when the inhibitory activity of humoral factors is eliminated. The combined application of chemo- and biotherapy based on anticancer vaccines of IEPOR series is an efficient and rather perspective method of inhibition of malignant tumor process. The optimal scheme of the combined therapy was developed that involved the administration of anticancer vaccines together with the application of chemotherapeutic agents. The augmentation of antitumor effect can be explained by the reduction of immunosuppressive activity of blood serum towards the effector cells of antitumor immunity, resulting from the additional signal to the immune system - use of anticancer vaccines.

Published in Journal of Cancer Treatment and Research (Volume 8, Issue 4)
DOI 10.11648/j.jctr.20200804.12
Page(s) 74-78
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Xenogeneic Anticancer Vaccine, Antimetastatic Efficiency, Combined Treatment

References
[1] Accolla RS, Buonaguro L, Melief C, Rammensee HG, Bassani-Sternberg M. Editorial: Novel Strategies for Anti-Tumor Vaccines. Front Immunol. 2020; 10: 3117. Published 2020 Jan 17.
[2] Charles J, Chaperot L, Hannani D et al. An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial. Oncoimmunology. 2020 Apr 12; 9 (1): 1738812.
[3] Guo C., Manjili M. H., Subjeck J. R. et al. (2013) Therapeutic cancer vaccines: past, present and future. Adv. Cancer Res., 119: 421–475.
[4] Zhao J., Huang Y., Liu D., Chen Y. (2014) Two hits are better than one: synergistic anticancer activity of α-helical peptides and Doxorubicin/epirubicin. Oncotarget., 6 (3): 1769–1778.
[5] Sheng Sow H., Mattarollo S. R. (2013) Combining low-dose or metronomic chemotherapy with anticancer vaccines. A therapeutic opportunity for lymphomas. OncoImmunology, 2 (12): e27058.
[6] Iinuma H., Fukushima R., Inaba T. et al. (2014) Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in sophageal cancer patients. J. Transl. Med., 12: 84.
[7] Gorbach O. I., Khranovska N. M., Skachkova O. V. et al. (2014) The chemoimmunotherapy based on dendritic cells and cisplatin in experiment. Biotechnol. Acta, 7 (4): 85–91.
[8] Ramakrishnan R., Assudani D., Nagaraj S. et al. (2010) Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. J. Clin. Invest., 120 (4): 1111–1124.
[9] Kim D., Monie A., Tsai Y-C. et al. (2008) Enhancement of CD4+ T-cell help reverses the Doxorubicin induced suppression of antigen-specific immune responses in vaccinated mice. Gene Ther., 15 (16): 1176–1183.
[10] Kepp O., Galluzzi L., Martins I. et al. (2011) Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev., 30: 61–69.
[11] Leisha A. Emens and Gary Middleton The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies Cancer Immunology Research May 2015, 3 (5): 436-443 р.
[12] Singh et al., Differential dendritic cell-mediated activation and functions of invariant NKT-cell subsets in oral cancer Oral Dis. 2015 Jan; 21 (1): e105-13.
[13] Ma Y, Mattarollo et al., CCL2/CCR2-Dependent Recruitment of Functional Antigen Presenting Cells into Tumors upon Chemotherapy. Cancer Res. 2014 Jan 15; 74 (2): 436-45.
[14] von Mehren M., Arlen P., Gulley J. Et al. (2001) The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patient with metastatic carcinoma. Clin. Cancer Res., 7: 1181–1191.
[15] Gulley J. L., Madan R. A., Schlom J. (2011) Impact of tumor volume on the potential efficacy of therapeutic vaccines. Current Oncol., 18: 150–157.
[16] Patent of Ukraine No. 57869. A method for producing of anticancer autovaccine. Potebnya G. P., Lіsovenko G. S., Cheremshenko N. L., Tanasііеnko O. A., Chekhun V. F.. (Ukraine) Appl. 15.06.2001; Publ. 15.07.2003; < Bull No. 7.
[17] J. Kraśko, K Zilionytė, A. Darinskas, N. Dobrovolskienė, A. Mlynska, S. Riabceva, I Zalutsky, Marina Derevyanko, V. Kulchitsky, O. Karaman, N. Fedosova, T. Symchych, G. Didenko, V. Chekhun, M. Strioga and V. Pašukonienė. / Post operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model. Oncology Letters. V. 15: 2018. P. 5098-5104.
[18] Patent of Ukraine No. 73671 (2005). A method for producing of anticancer vaccine and method for oncological patients treatment / Potebnya G. P., Lіsovenko G. S., Cheremshenko N. L., Semernikova L. I., Didenko G. V., Leshchenko Yu. M., Zavertylenko S. P., Chekhun V. F. (Ukraine); 15.08.2005, Bull. No. 8.
[19] Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ Neutrophil–lymphocyte ratios as a prognostic factor in colorectal cancer. J Surg Oncol 91: 181–184.
[20] Keizman D, Gottfried M, Ish-Shalom M et al Pretreatment neutrophil-to-lymphocyte ratios in metastatic castration resistant prostate cancer patient treated with ketoconazole: association with outcome and predictive nomogram. Oncologist 17 (12): 1508–1514.
[21] Sunbul M, Gerin F, Durmus E, Kivrak T, Sari I, Tigen K, etal. Neutrophil to lymphocyte and platelet to lymphocyte ratios in patient with dipper versus non-dipper hypertension. Clin Exp Hypertens. 2014; 36 (4): 217-21.
[22] Seropian IM, Romeo FJ, Pizarro R, Vulcano NO, Posatini RA, Marenchino RG, Berrocal DH, Belziti CA Neutrophil-to-lymphocyte ratios and platelet-to lymphocyte ratios as predictors of survival after heart transplantation. // ESC Hear tFail. 2018 Feb; 5 (1): 149-156.
[23] Ohno M., Abe T. (1991) Rapid colorimetric assay for the quantification of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). J. Immunol. Meth., 145: 199–203.
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    Olena Kruts, Volodymyr Konovalenko, Volodymyr Bazas, Sergii Konovalenko, Gennadii Didenko, et al. (2020). Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma. Journal of Cancer Treatment and Research, 8(4), 74-78. https://doi.org/10.11648/j.jctr.20200804.12

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    Olena Kruts; Volodymyr Konovalenko; Volodymyr Bazas; Sergii Konovalenko; Gennadii Didenko, et al. Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma. J. Cancer Treat. Res. 2020, 8(4), 74-78. doi: 10.11648/j.jctr.20200804.12

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    AMA Style

    Olena Kruts, Volodymyr Konovalenko, Volodymyr Bazas, Sergii Konovalenko, Gennadii Didenko, et al. Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma. J Cancer Treat Res. 2020;8(4):74-78. doi: 10.11648/j.jctr.20200804.12

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  • @article{10.11648/j.jctr.20200804.12,
      author = {Olena Kruts and Volodymyr Konovalenko and Volodymyr Bazas and Sergii Konovalenko and Gennadii Didenko and Oleksandr Lytvynenko and Anna Artamonova and Oksana Gerashchenko},
      title = {Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma},
      journal = {Journal of Cancer Treatment and Research},
      volume = {8},
      number = {4},
      pages = {74-78},
      doi = {10.11648/j.jctr.20200804.12},
      url = {https://doi.org/10.11648/j.jctr.20200804.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20200804.12},
      abstract = {Anticancer xenogeneic vaccine – is an agent, containing antigens of embryonic origin that underwent biotransformation under the action of cytotoxic proteins of В. subtilis B-7025. Anticancer efficacy of the vaccine is implemented by breaking immune system tolerance to own tumor antigens due to the antigenic similarity between tumor and embryonic proteins. The experiments were conducted in Wistar female rats (age 2.5 months and weight 200-220 g, bred at the animal house of R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology). The care and use of the experimental animals have been performed in accordance with generally accepted international rules for conducting experiments in experimental animals. As an experimental tumor model, we have used Walker carcinosarcoma. In preclinical and clinical trials, success has been demonstrated in the use of a combination of anticancer vaccines with chemotherapy to achieve a synergistic effect, even if the dose and schedule of administration of the agents needed to be optimized. It has been shown that some drugs (doxorubicin, cyclophosphamide, docetaxel) induce immunological death of tumor cells, increase the expression of tumor-associated antigens, HLA-peptide complexes, thus sensitizing the tumor in vaccine-induced T-cell killing. It was determined that simultaneous administration of anticancer vaccines (regardless of the antigenic composition) and Doxorubicin resulted in a significant increase of survival and average lifespan of the experimental animals. The treated animals at the end of the experiment presented with increased cytotoxicity of lymphocytes and macrophages (both direct and antibody-dependent), suggesting a reduced level of immunosuppression in experimental animals. In the group of rats, receiving Dox, the serum had no effect on the activity of lymphocytes. These data suggest that during the development of tumor the serum accumulates humoral factors, capable of blocking lymphocyte activity. Yet, as a result of additional activation (due to anticancer vaccines), the conditions are provided when the inhibitory activity of humoral factors is eliminated. The combined application of chemo- and biotherapy based on anticancer vaccines of IEPOR series is an efficient and rather perspective method of inhibition of malignant tumor process. The optimal scheme of the combined therapy was developed that involved the administration of anticancer vaccines together with the application of chemotherapeutic agents. The augmentation of antitumor effect can be explained by the reduction of immunosuppressive activity of blood serum towards the effector cells of antitumor immunity, resulting from the additional signal to the immune system - use of anticancer vaccines.},
     year = {2020}
    }
    

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    T1  - Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma
    AU  - Olena Kruts
    AU  - Volodymyr Konovalenko
    AU  - Volodymyr Bazas
    AU  - Sergii Konovalenko
    AU  - Gennadii Didenko
    AU  - Oleksandr Lytvynenko
    AU  - Anna Artamonova
    AU  - Oksana Gerashchenko
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    PY  - 2020
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    DO  - 10.11648/j.jctr.20200804.12
    T2  - Journal of Cancer Treatment and Research
    JF  - Journal of Cancer Treatment and Research
    JO  - Journal of Cancer Treatment and Research
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    EP  - 78
    PB  - Science Publishing Group
    SN  - 2376-7790
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    AB  - Anticancer xenogeneic vaccine – is an agent, containing antigens of embryonic origin that underwent biotransformation under the action of cytotoxic proteins of В. subtilis B-7025. Anticancer efficacy of the vaccine is implemented by breaking immune system tolerance to own tumor antigens due to the antigenic similarity between tumor and embryonic proteins. The experiments were conducted in Wistar female rats (age 2.5 months and weight 200-220 g, bred at the animal house of R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology). The care and use of the experimental animals have been performed in accordance with generally accepted international rules for conducting experiments in experimental animals. As an experimental tumor model, we have used Walker carcinosarcoma. In preclinical and clinical trials, success has been demonstrated in the use of a combination of anticancer vaccines with chemotherapy to achieve a synergistic effect, even if the dose and schedule of administration of the agents needed to be optimized. It has been shown that some drugs (doxorubicin, cyclophosphamide, docetaxel) induce immunological death of tumor cells, increase the expression of tumor-associated antigens, HLA-peptide complexes, thus sensitizing the tumor in vaccine-induced T-cell killing. It was determined that simultaneous administration of anticancer vaccines (regardless of the antigenic composition) and Doxorubicin resulted in a significant increase of survival and average lifespan of the experimental animals. The treated animals at the end of the experiment presented with increased cytotoxicity of lymphocytes and macrophages (both direct and antibody-dependent), suggesting a reduced level of immunosuppression in experimental animals. In the group of rats, receiving Dox, the serum had no effect on the activity of lymphocytes. These data suggest that during the development of tumor the serum accumulates humoral factors, capable of blocking lymphocyte activity. Yet, as a result of additional activation (due to anticancer vaccines), the conditions are provided when the inhibitory activity of humoral factors is eliminated. The combined application of chemo- and biotherapy based on anticancer vaccines of IEPOR series is an efficient and rather perspective method of inhibition of malignant tumor process. The optimal scheme of the combined therapy was developed that involved the administration of anticancer vaccines together with the application of chemotherapeutic agents. The augmentation of antitumor effect can be explained by the reduction of immunosuppressive activity of blood serum towards the effector cells of antitumor immunity, resulting from the additional signal to the immune system - use of anticancer vaccines.
    VL  - 8
    IS  - 4
    ER  - 

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Author Information
  • Laboratory of Oncoimmunology and Design of Antitumor Vaccines, R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine

  • Tumor Monitoring and Therapy Design Department, R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine

  • Surgery Department, Kyiv City Oncology Center, Kyiv, Ukraine

  • Tumor Monitoring and Therapy Design Department, R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine

  • Laboratory of Oncoimmunology and Design of Antitumor Vaccines, R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Kyiv, Ukraine

  • Department of Skin and Soft Tissue Tumors, Institute of Cancer of the Ministry of Health of Ukraine, Kyiv, Ukraine

  • Department of Pharmacological and Biological Chemistry and Pharmacognosy, Kyiv Medical University, Kyiv, Ukraine

  • Surgery Department, Kyiv City Oncology Center, Kyiv, Ukraine

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