The Study On The Effects Of Conventional Drugs On NK Cell Cytotoxicity And NK Cell Immunotherapy

NK cell immunotherapy is an important classification of tumor immunotherapy.NK cell immunotherapy has shown great potential and broad prospects in the field ofantitumorsr due to its powerful tumor-killing function and immunomodulatory effect.At present,the discovery and development of innovative drugs for NK cell immunotherapy has been carried out,and many valuable results have been achieved.However,the discovery and development of drugs are difficult,with a development cycle of more than 10 years and a failure rate of 97%.The strategy of conventional drugs in new use can circumvent the arduous and time-consuming process of innovative drug development,improving the success rate of research and development.With the increasing risk of the discovery and development of innovative drugs,the strategy of conventional drugs in new use has gradually become one of the most concerned topics in the field of drug discovery and development.Therefore,it is of great practical significance to apply conventional drugs to NK cell immunotherapy.The cytotoxicity of NK cells is an important effector mechanism in anti-tumor therapy,and the monitoring of its markers is an important way to understand the anti-tumor effect of NK cells and to facilitate the efficient development of NK cell immunotherapy.In summary,this study focused on the influence of conventional drugs on the killing function of NK cells and applied them in NK cell immunotherapy to improve the antitumor effect,and a fluorescent probe was constructed to monitor the effects of drugs on markers of NK-cell cytotoxicity.The specific research content is described as follows:1.The effect of conventional drugs on NK-cell cytotoxicity was studied.Drugs are divided into three categories: drugs related to blood lipids,blood pressure and blood sugar;drugs that have anticancer effects;antibiotics,antiviral drugs.On this basis,drugs that can enhance the killing effect of NK cells were distinguished,such as paclitaxel,aspirin,amoxicillin,atorvastatin,acarbose and artemisinin.These cell-level studies could not only unlock new uses for traditional drugs,but also lay the groundwork for new ways to enhance NK cell-killing function.2.The mechanism of amoxicillin enhancing the killing effect of NK cells and its application in adjuvant NK cell immunotherapy are studied.It was found that amoxicillin could promote the initiation of the cytolytic program of target cell-deficient NK-92 mi cells and improve the degranulation level in target cell-containing NK-92 mi cells.Moreover,amoxicillin did not significantly kill MCF-7 cells during the process.In a mouse model of breast cancer,amoxicillin was applied to adjuvant NK cell immunotherapy,and the results showed that amoxicillin could enhance the antitumor effect of NK cell immunotherapy.These studies suggest that amoxicillin as a strategy for adjuvant NK cell immunotherapy has potential application value in the field of tumor therapy.3.In order to monitor the m RNA expression of cytotoxic intracellular activation markers perforin and granzyme B m RNA in NK-92 mi cells,a gold nanosphere fluorescent probe based on poly A was designed and assembled.The probe has good intracellular imaging effects and biocompatibility.It has been confirmed that the poly A-based gold nanosphere fluorescent probe can be used to evaluate the induction effect of amoxicillin or IL-2 on the m RNA expression of perforin and granzyme B in NK-92 mi cells.The probe can provide an effective tool for the detection and imaging of intracellular targets in NK cells.