4 research outputs found

    Оптимизация аутологичных дендритно-клеточных вакцин для лечения больных злокачественными новообразованиями

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    Immunobiological features of the dendritic cells (DC) were studied for the production of DC-vaccine (DCV) optimization. DC were differentiated in vitro in GM-CSF (previously studied concentration 72 ng/ml and IL-4 0–45 ng/ml containing medium. GM-CSF compounds by Pharmsynthez (Russia) and Cell Genix (Germany) and IL-4 by Cell Genix (Germany) were used. Comparative assays of mature and immature DC immunophenotype using different GM-CSF compounds was performed. CD1а, CD83, CD86, CD80, CCR7 и HLA DR are recommended optimal markers of DC for the standardization of technologic process. Flow cytometry and immunocytochemistry assays revealed no differences in mature DC markers expression (p>0,05). This indicates the expediency of Pharmsynthez (Russia) GM-CSF usage for DCV production. Optimal IL-4 concentrations (5–15 ng/ml) providing qualitative characteristics for DCV production were found using second level one-way polynomial model.Исследованы иммунобиологические характеристики дендритных клеток (ДК) для оптимизации технологии получения дендритно-клеточных вакцин (ДК-вакцин). Проведен сравнительный анализ иммунологического фенотипа незрелых и зрелых ДК, дифференцированных in vitro в присутствии ростового фактора GM-CSF (CellGenix, Германия) и ГМ-КСФ (Фармсинтез, Россия) в ранее изученной концентрации 72 нг/мл, и IL-4 (CellGenix, Германия) в интервале концентраций от 0 до 45 нг/мл. Для стандар- тизации технологического процесса получения вакцинных ДК рекомендуется использовать оптимальную панель моноклональных антител: CD14, CD1а, CD83, CD86, CD80, CCR7, HLA DR. Результаты проточной цитометрии и иммуноцитохимического анализа показали отсутствие достоверных различий в экспрессии маркеров зрелых ДК (p>0,05), что свидетельствует о целесообразности использования ростового фактора ГМ-КСФ (Фармсинтез, Россия) для приготовления противоопухолевых вакцин на основе ДК. С помощью однофакторных полиномиальных моделей второго порядка установлен оптимальный интервал концентрации IL-4 для дифференцировки ДК от 5 до 15 нг/мл

    ИСПОЛЬЗОВАНИЕ СИСТЕМ RECIST 1.1 И irRC ДЛЯ ОЦЕНКИ ОТВЕТА НА ТЕРАПИЮ ИПИЛИМУМАБОМ ИЛИ ДЕНДРИТНОКЛЕТОЧНЫМИ ВАКЦИНАМИ У ПАЦИЕНТОВ С ДИССЕМИНИРОВАННОЙ МЕЛАНОМОЙ КОЖИ

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    Special systems were developed for response assessment of immunooncology drugs. The role and benefits of particular system in assessing the efficacy of different immunotherapy methods are not clear yet. The objective of this study is to compare the responses on ipilimab (IPI) or dendritic cell vaccines (DCV) therapy by RECIST 1.1 and irRC criteria. Eighty two patients with unresectable disseminated or locally advanced stage III-IV melanoma were included. Fifty-five patients were treated with IPI and 27 – with DCV at the N.N. Petrov National Medical Research Center of Oncology from 2007 to 2016. Response by each system was compared to overall survival (OS). Response by both systems was a good marker for OS in IPI group (p=0,0001 for both systems) but not in DCV group (p=0,357 for RECIST and p=0,411 for irRC). Discrepancies in responses by different systems were detected in 5 patients in the IPI group and in 5 patients in the DCV group (p>0.05). The median of OS in IPI patients with PD by both systems was 8.8 mo. In case of mixed responses, (RECIST progression disease (PD) and irRC stable disease) OS in IPI group was 29.1+ mo, 16.7 mo. In the case of SD by RECIST and PD by irRC OS was 11.6+ mo. One patient with PD by RECIST and partial response by irRC lived 16.3 mo. OS in DCV group was 9.5+, 8.7, 15.3, 29.7 mo. in patients with mixed responses (PD+SD); 15,7 mo. in patient with SD by RECIST and PR by irRC. There was a trend to better overall survival of patients with PD according to the RECIST 1.1 and the absence of PD by irRC system in comparison with the PD by both systems in the treatment of IPI was revealed. In the DCV group the same pattern wasn’t found. Thus, both the RECIST 1.1 system and the irRC system are good surrogate markers for the overall survival. SD in patients receiving DCV cannot be considered a good response to therapy, since it does not improve the OS in comparison with patients who has PD by the same system. The irRC system allows to extract a subgroup of patients with better overall survival from patients with PD by RECIST among those who receive IPI but not DCV for systemic therapy of melanoma.Для оценки эффективности новых методов иммунотерапии были созданы специализированные системы оценки объективного ответа на лечение. Однако роль и преимущества использования конкретной методики до сих пор не ясны. Нами проведено ретроспективное сравнение оценки эффективности различных по механизму действия методов иммунотерапии – ипилимумаба (IPI) и аутологичной дендритноклеточной вакцины (DCV) – по системам RECIST 1.1 и irRC. В исследование включено 82 пациента с диссеминированной или местнораспространенной нерезектабельной меланомой кожи III–IV стадии, получавших IPI (n=55) или DCV (n=27). Оценку ответа по каждой из систем сопоставляли с общей выживаемостью больных (OS). Эффект лечения по любой системе позволял прогнозировать OS больных, получавших IPI (р=0,0001 для каждой системы), но не DCV (р=0,357 и p=0,411 для RECIST 1.1 и irRC соответственно). Частота расхождений ответов на лечение между разными системами оценки была сопоставима для IPI и DCV (10 % и 19 % соответственно, р>0,05). В группе IPI медиана OS при прогрессировании заболевания (PD) по двум системам составила 8,8 мес, PD по RECIST 1.1 и стабилизация заболевания (SD) по irRC OS наблюдалась у 2 больных с ОВ – 29,1+ мес и 16,7 мес. При обратной ситуации у 2 больных OS составила 11,6+ и 12 мес. Медиана OS при SD по 2 системам – 25,5 мес, при объективном ответе – 35,2 мес. В группе DCV у пациентов с PD по обеим системам (медиана OS – 11,3 мес) показатели OS не отличались от SD (9,8 мес). При смешанном ответе (PD по одной системе и SD по другой) показатели OS у больных составили 29,7 мес, 8,7 мес, 9,5+ мес. При объективном ответе наблюдались лучшие показатели OS: 70,3+ мес, 9,5 мес, 102,9+ мес. Таким образом, расхождение оценок ответа по системам RECIST 1.1 и irRC одинаково часто встречается при различных методах иммунотерапии, но имеет различное значение для прогнозирования OS. Требуется отдельная оценка применимости системы irRC для иммунопрепаратов с разными механизмами действия

    Autologous Dendritic Cell Vaccine Optimization for Therapy of Patients with Disseminated Malignant Ne

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    Immunobiological features of the dendritic cells (DC) were studied for the production of DC-vaccine (DCV) optimization. DC were differentiated in vitro in GM-CSF (previously studied concentration 72 ng/ml and IL-4 0–45 ng/ml containing medium. GM-CSF compounds by Pharmsynthez (Russia) and Cell Genix (Germany) and IL-4 by Cell Genix (Germany) were used. Comparative assays of mature and immature DC immunophenotype using different GM-CSF compounds was performed. CD1а, CD83, CD86, CD80, CCR7 и HLA DR are recommended optimal markers of DC for the standardization of technologic process. Flow cytometry and immunocytochemistry assays revealed no differences in mature DC markers expression (p>0,05). This indicates the expediency of Pharmsynthez (Russia) GM-CSF usage for DCV production. Optimal IL-4 concentrations (5–15 ng/ml) providing qualitative characteristics for DCV production were found using second level one-way polynomial model

    RECIST 1.1 AND irRC FOR RESPONSE ASSESMENT IN PATIENTS WITH DISSEMINATED CUTANEOUS MELANOMA TREATED WITH IPILIMUMAB OR DENDRITIC CELL VACCINE

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    Special systems were developed for response assessment of immunooncology drugs. The role and benefits of particular system in assessing the efficacy of different immunotherapy methods are not clear yet. The objective of this study is to compare the responses on ipilimab (IPI) or dendritic cell vaccines (DCV) therapy by RECIST 1.1 and irRC criteria. Eighty two patients with unresectable disseminated or locally advanced stage III-IV melanoma were included. Fifty-five patients were treated with IPI and 27 – with DCV at the N.N. Petrov National Medical Research Center of Oncology from 2007 to 2016. Response by each system was compared to overall survival (OS). Response by both systems was a good marker for OS in IPI group (p=0,0001 for both systems) but not in DCV group (p=0,357 for RECIST and p=0,411 for irRC). Discrepancies in responses by different systems were detected in 5 patients in the IPI group and in 5 patients in the DCV group (p>0.05). The median of OS in IPI patients with PD by both systems was 8.8 mo. In case of mixed responses, (RECIST progression disease (PD) and irRC stable disease) OS in IPI group was 29.1+ mo, 16.7 mo. In the case of SD by RECIST and PD by irRC OS was 11.6+ mo. One patient with PD by RECIST and partial response by irRC lived 16.3 mo. OS in DCV group was 9.5+, 8.7, 15.3, 29.7 mo. in patients with mixed responses (PD+SD); 15,7 mo. in patient with SD by RECIST and PR by irRC. There was a trend to better overall survival of patients with PD according to the RECIST 1.1 and the absence of PD by irRC system in comparison with the PD by both systems in the treatment of IPI was revealed. In the DCV group the same pattern wasn’t found. Thus, both the RECIST 1.1 system and the irRC system are good surrogate markers for the overall survival. SD in patients receiving DCV cannot be considered a good response to therapy, since it does not improve the OS in comparison with patients who has PD by the same system. The irRC system allows to extract a subgroup of patients with better overall survival from patients with PD by RECIST among those who receive IPI but not DCV for systemic therapy of melanoma
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