7 results about "Cell killing" patented technology

The application discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

An anti-tumor pharmaceutical composition based on immune checkpoint blocking and a use thereof. The anti-tumor pharmaceutical composition comprises: paroxetine hydrochloride and a T cell enhancer, the T cell enhancer being at least one of vitamin E and thymosin. By means of a series of in vivo and in vitro experiments, it was found for the first time that cannabidiol and paroxetine hydrochloride can effectively reduce the expression of PD-L1 on a tumor cell membrane, thereby blocking the PD-1 / PD-L1 signaling pathway and enhancing the effect of T cells in killing tumor cells. T cell enhancer added on this basis can further increase the number and activity of T cells and significantly enhance the killing ability of T cells after relief from immunosuppression, greatly improving the anti-tumor effect of a drug. The components cannabidiol, paroxetine hydrochloride, and vitamin E+thymosin of the pharmaceutical composition can have a synergistic effect to improve the anti-tumor effect.

This invention belongs to the field of biomedicine and tumor immunotherapy technology, specifically relating to a monoclonal antibody targeting the immune checkpoint molecule CD276 (B7-H3) and its applications. The applicant conducted immunization and screening work around the human CD276 antigen, selecting two representative monoclonal antibody clones, 2B2-1 and 5G4-2, from multiple candidate antibodies. The nucleotide and amino acid sequences of their heavy and light chain variable regions were determined, and their performance in flow cytometry, T-cell killing assays, immunohistochemistry, ELISA, and Biacore affinity assays was systematically evaluated. Experimental results show that the above antibodies can specifically recognize and bind to CD276, efficiently distinguish between CD276-high and low-expressing cells, and enhance the killing activity of T cells against CD276-high expressing tumor cells in an in vitro co-culture system. This provides an excellent antibody backbone for the subsequent construction of diagnostic kits, ADC drugs, or bispecific antibodies.

This invention belongs to the field of biomedical technology, specifically relating to an anti-tumor nanomaterial, its preparation method, and its application. The anti-tumor nanomaterial is formed by in-situ growth of calcium peroxide on the surface of black phosphorus nanosheets to create hierarchical black phosphorus-calcium peroxide nanosheets, followed by coating the surface of these composite nanosheets with hyaluronic acid. After entering tumor cells, the anti-tumor nanomaterial releases calcium ions and hydrogen peroxide, triggering an abnormal increase in calcium ions and oxidative stress within the cells, thereby causing mitochondrial dysfunction and inducing tumor cell death. Simultaneously, the released calcium ions combine with phosphate ions produced by the degradation of black phosphorus, forming calcium phosphate mineralization deposits within the tumor tissue, inducing tumor biocalcification. Changes in calcium signaling and the oxidative stress process can also promote the infiltration and activation of immune cells, thereby regulating the tumor immune microenvironment and achieving a synergistic effect of cell killing, biocalcification induction, and immune regulation within tumor tissue.

The application provides a method for enhancing the expansion and activation of memory-like NK cells, and belongs to the technical field of cell culture. The application provides a method for obtaining strong memory-like NK cells, which comprises using complete culture medium, IL-2, IL-12, IL-15, IL-18, sodium alpha-ketoglutarate and DOT1L inhibitor; the concentration of the sodium alpha-ketoglutarate is 0.1-2 mM, and the concentration of the DOT1L inhibitor is 10-100 nM. The addition of low-concentration sodium alpha-ketoglutarate in the complete culture medium of memory-like NK cells can promote the in-vivo and in-vitro proliferation capacity of the memory-like NK cells. The addition of low-concentration DOT1L inhibitor in the late culture stage can further enhance the killing function of the memory-like NK cells by inhibiting H3K79me2 / 3, etc., so that memory-like NK cells with a larger number and stronger killing capacity are obtained.

The present invention relates to the identification of key residues within mouse lgG3 antibodies (mAbs) that are responsible for intermolecular cooperativity and their transfer into lgG1 antibodies in order to enhance their functional affinity and direct cell killing.