COMPARISON OF THE EFFICACY OF DIFFERENT REGIMENS OF XENOGENEIC CANCER VACCINE ON MODELS OF METASTATIC TUMOR GROWTH
Keywords:
xenogeneic cancer vaccine, endogene interferon inductor, antimetastatic efficiency, melanoma B-16, Lewis lung carcinoma, cytotoxic activity, cytokines.Abstract
Summary. Objective: study of the possibility of increasing the effectiveness of antitumor vaccine therapy with the help of endogene interferon inductor (EII) on the metastatic models of the tumor
process. Object and methods: the study was conducted on C57Bl/6 mice, operated on the B-16 melanoma or Lewis lung carcinoma (LLC). Experiment scans and doses of drug administration were
the same for both types of tumors model. Xenogeneic cancer vaccine (XCV) (total protein concentration
[C] = 0.3 mg/ml) was administered subcutaneously
at 0.3 ml/mouse, three times at 3-day intervals after tumor removal. EII was administered per os before tumor removal three times (0.06 mg/mouse). The
antimetastatic activity was evaluated by the metastasis inhibition index. Immunological study included determination of cytotoxic activity of cellular immunity and blood serum effector (MTT-test); level of
IL-4, IL-10, IFN-γ (IFA-method). Statistical processing of the results was performed using the StatSoft STATISTICA 7.0 program using Student’s t-criterion and correlation coefficients (r). Results: the
antimetastatic effectiveness of XCV, designed basing
on the antigens of embryonic rat nervous tissue, depends on the type of tumor model and mode of drug
administration: for melanoma B-16, XCV is the most
efficient when administered in monomode; for Lewis lung carcinoma — when XCV is used combined
with EII. The study on the activity of major effectors of antitumor immunity showed that these results
are caused by cytotoxic activity of nonspecific immunity cells: natural killer cells and macrophages
(melanoma B-16) or only macrophages (LLC), as
well as by prevalence of cytokine content from the
first type helper T-lymphocytes in the serum of vaccinated animals, which is evidenced by the increase
of the IFN-γ/IL-4 ratio throughout the whole observation period. This cytokine balance is likely to
ensure the full functioning of the cell antitumor immunity effectors providing the antimetastatic effect
of the studied vaccine. Conclusion: the obtained results may constitute an experimental substantiation
of the individualized use of cancer vaccines in monomode or in combination with EII in immunotherapy of malignant tumors of different immunogenicity
in clinical practice.
References
Schlom J, Arlen PM, Gulley JL. Cancer vaccines: moving beyond current paradigms. Clin Cancer Res 2007; 13: 3776–82.
Лесной ИИ, Сидор РИ, Храновская НН и др. Роль различных групп аналгетиков в безопасности периоперационного обезболивания онкохирургических больных. Біль, знеболювання і інтенсивна терапія 2016; (1): 61–70.
Гриневич ЮА. Пути развития иммунотерапии в онкологии. Обзор исследований, выполненных в Национальном институте рака 2016; (1(21)): 76–80.
Ялкут СИ, Потебня ГП. Биотерапия опухолей. К.: КнигаПлюс, 2010. 472 с.
Прохач НЭ. Иммунотерапия в лечении онкологических больных. Международный мед журн 2003; (2): 112–6.
Бровкина АФ, Кешелава ВВ, Сологуб ВК и др. Ксеновакцинация впрофилактике метастазов увеальной меланомы. Вестник РНЦРР 2011; (11) (http://vestnik.rncrr.ru/vestnik/v11/papers/ brovk_v11.htm).
Posh C, Weihsengruber F, Bartsch, at al. Low dose inhalation of IL-2 bio-chemotherapy for treatment of pulmonary metastases in melanoma patients. Br J Cancer 2014; 110 (6): 1427–32.
Itoh K, Yamada A, Mine T, Noguchi M. Recent advances in cancer vaccines: an overview. Jpn J Clin Oncol 2009; 39 (2): 73–80.
Slingluff CL Jr, Petroni GR, Yamshchikov GV, et al.Immunologic and clinical outcomes of vaccination with a multiepitope melanoma peptide vaccine plus low-dose interleukin-2 administered either concurrently or on a delayed schedule. J Clin Oncol 2004; 22 (22): 4474–85.
Kameshima H, Tsuruma T, Kutomi G, et al.Immunotherapeutic benefit of α-interferon (IFNα) in survivin 2B-derived peptide vaccination for advanced pancreatic cancer patients. Cancer Sci 2013; 104 (1): 124–9.
Rizza P, Moretti F, Belardelli F. Recent advances on the immunomodulatory effects of IFN-alpha: implications for cancer immunotherapy and autoimmunity. Autoimmunity 2010; 43 (3): 204–9.
Чувиров ДГ, Ярцев МИ.Иммуномодуляторы впедиатрии. Педиатрия 2009; (1): 62–7.
Жильчук ВЄ, Воронцова АЛ, Кудрявець ЮЙ та ін. Ефективність комплексної терапії хворих нарак молочної залози звикористанням аутовакцини та інтерферону. Вісн наук досліджень 2009; (2): 36–8.
Sunkara PS, Prakash NJ, Rosenberger AL, et al. Potentiation of antitumor and antimetastatic activities of alpha-difluoromethylornithine by interferon inducers. Cancer Res 1984; 44 (7): 2799–802.
Fedosova NI, Voeykova IM, Karaman OM, et al. Cytotoxic activity of immune cells following administration of xenogeneic cancer vaccine in mice with melanoma B-16. Exp Oncol 2015; 37 (2): 130–4.
Федосова НІ, Караман ОМ, Воєйкова ІМ та ін. Ефективність неоад’ювантного застосування аміксину вякості засобу імунотерапії меланоми В-16 у мишей лінії C57BL. Клінічна імунологія. Алергологія. Інфектологія 2016; (6(95)): 46–51.
Кожем’якін ЮМ, Хромов ОС, Філоненко МА, Сайфетдінова ГА. Науково-практичні рекомендації з утримання лабораторних тварин та роботи з ними. Київ, 2002. 179 с.
Экспериментальная оценка противоопухолевых препаратов в СССР и США // Под ред: ЗП Софьиной, АВ Сыркина. М: Медицина, 1980. 79 с.
Kellar A, Egan C, Morris D. Preclinical murine models for lung cancer: clinical trial applications. Bio Med Res Int 2015; 2015 (2015): Art ID 621324, 17 p.
Потебня ГП, Воєйкова ІМ, Юдіна ОЮ. Спосіб одержання протипухлинної вакцини (Україна). Патент на корисну модель №78756 (UA); заявка №u201212402 від 30.10.2012; Опубл. 25.03.2013. Бюл. №6.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55–63.
Ковбасюк СА, Юдин ВМ, Кравченко СП. Иммуномудулирующее влияние циклофосфана приразличных схемах введения его мышам. Цитология 1985; (3): 316–21.
Сиденко АВ, Вишняков ВВ, Исаев СМ. Теория статистики. Учебник. М: МАКС-Пресс, 2011. 343 с.
Балдуева ИА. Иммунологические особенности взаимоотношения опухоли и организма при меланоме. Практ онкол 2001; (4 (8)): 37–41.
Paradkar PH, Joshi JV, Mertia PN, еt al. Role of cytokines in genesis, progression and prognosis of cervical cancer. Asian Pacific J Cancer Prevent 2014; 15 (9): 3851–64.
Лямина СВ, Малышев ИЮ. Поляризация макрофагов в современной концепции формирования иммунного ответа. Фундаментальные исследования 2014; (10 (5)): 930–5.
