REFLOT® has a direct antitumor effect in vitro and in vivo on different lines of tumor cells. According to the spectrum of cytotoxic and cytostatic effects on tumor cells, the drug corresponds to the tumor necrosis factor α (TNF) in humans, however REFNOT® has more than 100 times less overall toxicity than TNF.
Mechanism of antitumor effect of REFNOT® in vivo includes several ways in which the drug destroys the tumor or stops its growth:
- the immediate effect of protein tumor necrosis factor-thymosin alpha 1 (TNF-T) on the target tumor cell through the corresponding receptors on its surface,resulting in apoptosis of the cell (cytotoxic action) or arrest of the cell cycle (cytostatic action). In the case of the last event, the cell becomes more differentiated and expresses a number of antigens;
- a cascade of chemical reactions, including activation of the coagulation system of blood and local inflammatory reactions caused by REFNOT®-activated endothelial cells and lymphocytes and leading to "hemorrhagic" necrosis of tumors;
- blocking of angiogenesis, leading to a decrease in germination by new vessels of a rapidly growing tumor and, as a consequence, to a decrease in blood supply up to necrosis of the tumor center;
- the effect of cells of the immune system, whose cytotoxicity was closely related to the presence of TNF-T molecules on their surface or the maturation / activation of these cells is associated with a response to TNF-T.
Combinations of REFNOT® from α2- or γ-interferons have a synergistic cytotoxic effect. REFLOT® increases the protective activity of recombinant interferon gamma 100-1000 times (against the virus of vesicular stomatitis).
REFLOT® increases the effectiveness of chemotherapy drugs: actinomycin D, cytosar, doxorubicin, against tumor cells weakly sensitive to them, eliminating this resistance. This allows us to consider REFNOT as a modifier of the antitumor effect of chemical cytostatics in cases of multiple drug resistance of tumor cells.
REFLOT® does not have a cytotoxic effect on normal cells, and in high concentrations in vitro stimulates the proliferation of spleen cells and lymph nodes. Enhances the production of antibodies to T-dependent antigens, has a stimulating effect on the cytotoxic effect of natural killer cells antitumor cells has a stimulatory effect on phagocytosis, enhances expression of class I MHC antigen H-2K Cd-4 and Cd-8, being a factor in the differentiation of T-helpers and T-killers.