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Information × Registration Number 0309U000120, 0106U012515 , R & D reports Title To develop the method for increase of antitumor resistance of organism using dendritic cells loaded with tumor antigen in experiment and to determine indications for its use in complex therapy of cancer patients popup.stage_title В експериментально-клінічних умовах встановити основні механізми протипухлинної дії дендритних клітин, навантажених пухлинним антигеном, в залежності від схеми застосування Head Khranovska Natalia, Registration Date 28-01-2009 Organization Ukrainian Research Institute of Oncology and Radiology popup.description2 Objective of the study – to develop the method of immunotherapy using dendritic cells loaded with tumor antigen on the model of metastasizing tumor and to determine indications for its use for the improvement of antitumor resistance of organism of the patients with malignancies. Dendritic cells (DC) generated in patients with ovarian, lung cancer and advanced melanoma on the level of surface molecules CD86, CD83 and HLA-DR belong to cells of medium rate of maturation and are suitable for use in immunotherapy. Maturation of DC increases with each infusion of DC-vaccine. Mature by phenotype peculiarities DCs are also mature functionally. Capability of DC activate lymphocytes in vitro, i.e. to induce increase of the level of expression of lymphoid markers CD3, CD4, CD8, CD56, CD16 and activation markers HLA-DR, CD25, CD71, CD38, CD95 was revealed. It evidence on their high functional activity and capability to induce generation of cytotoxic T-lymphocytes in vivo. It is approved that mechanochemically heterogenized tumor cells (MCH TC) at a greater extent initiate maturing DC as compared with usual tumor antigen. Increase of nuclei brightness, area of cytoplasma, nucleo-cytoplasmic ratio and decrease of heterogeneity of DC nuclei evidence on this. The most optimal concentration of MCH TC for DC loading is 0,05 mg/ml.It is revealed that DC vaccine therapy potentiates increase of cytotoxic activity of natural killer cells in patients with lung cancer and melanoma. Appearance of antigen- specific immune response under the effect of immunotherapy occurs after 3-4 infusions of DC loaded with TA. Increase of inhibition rate of leukocyte migration on TA stimulation in reaction of inhibition of leukocyte migration and increase of proliferating lymphocytes after co-cultivation with TA in reaction of blast transformation of lymphocytes evidence on that. After 3-4 infusion of DC loaded with TA changeover from Т х 2 type of immune response to Т х 1 type takes place, increase of IFN-? secretion, decrease of Il-4occur that evidence on activation of antigen-specific cell immune response in patients that is a basis of antitumor immunity. Indices under investigation can be used as markers of immunotherapy efficacy, both potential and duration of immune response. They allow determination of immunotherapy duration (number of courses) for individual patient that is why they should be considered to be a necessary compound in the dynamic monitoring of therapy efficacy. It is revealed that DC vaccine therapy cause immunologic response in 75 % of patients. In patients with long-term remission (over 1 year) and in patients with progression of disease different immunologic responses on DC vaccine therapy take place: in patients with a remission total amount of lymphocytes and activated T lymphocytes (HLA-DR+, CD95+, CD71+ та CD38+, для CD95+ - p<0,05) increases, in patients with progression of disease significant decrease of their amount occurs. Increase of amount of CD95+ lymphocytes can be additional marker for monitoring of DC vaccine therapy efficacy. Corse treatment with DC loaded with TA is not accompanied by the development of essential side or toxic reactions. DC vaccine therapy promotes 31% (р= 0,01) increase of 2 year survival of ovarian cancer patients, 27 % increase of lung cancer patients as compared with controls. Product Description popup.authors popup.nrat_date 2020-04-02 Close