Registration Number
0213U001856,
0110U002206
, R & D reports
Title
Develop of specific and nonspecific combinatorial immunotherapy method in experiment and demostrate definition in its application for complex treatment of cancer patients
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Head
Khranovska Natalia,
Registration Date
21-02-2013
Organization
Ukrainian Research Institute of Oncology and Radiology
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Object - dendritic cell vaccines, interferon-gamma, low dose of cyclophosphamide, interferon-gamma, mice with experimental tumor (Lewis lung carcinoma), level of mRNA expression. Goal: develop the method of combinatorial immunotherapy based on autologic dendritic cell vaccines, low dose of cyclophosphamide and interferon-gamma and define of the indications for use it in complex treatment of cancer patients. Methods - multi-color flow cytometry, immunological, molecular-genetic, statistical. Equipment - flow cytometer FACSCalibur, centrifuges "ОПН-3", microscope, scales "ВТ", spectrophotometer "Nano Drop 1000", 7500 Real-Time PCR Systems. It was established that the grow of Lewis lung carcinoma (LLC) характеризується significant decrease mRNA expression level of transporters ТАР1 and ТАР2 and increase mRNA expression level of immunosuppressive cytokines IL-10, TGF-? and growth factor VEGF. The new scheme of combinatorial immunotherapy based on dendritic cells (DC) vaccine, low dose of cyclophosphamide (CF) and interferon-gamma (IFN-gamma) was developed. The scheme involves the injection of CF daily for 5 days (total dose 400 mg/kg), start from 5th day after transplantation of LLC, then after 2 days the injection of IFN-gamma (4 injection at 2-day intervals) and DC-vaccine, start from 3 days after chemotherapy CF (3 injection at 3-day intervals). It was established that administration of DC-vaccine in combination with low dose of CF and IFN-gamma promotes significant inhibition of metastasis. It was noticed that the low-dose metronomic CF chemotherapy induces a selectivity reduced of T-regulatory (Т-reg) lymphocytes in spleen and decrease the mRNA expression level of TGF-beta in splenocytes and tumor. Combinatorial immunotherapy promotes a modulation of Т-cell immune response to Т helper 1 type in lymph nodes and activation of non-specific immune response. The new scheme of combinatorial immunotherapy based on dendritic cells vaccine, low dose of cyclophosphamide and IFN-gamma was developed in experiment. This scheme in future could be recommended for use in complex treatment of cancer patients to prevent relapses and metastases. The indications for use it in complex treatment of patients with lung and kidney cancer were defined.
Product Description
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Іонкіна Н.В.
Свергун Н.М.
Скачкова О.В.
Храновська Н. М.
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2020-04-02