76 results about "Cell kill" patented technology

The invention discloses a culture method for improving proliferation and differentiation capacity of NK (Natural Killer) cells based on angelica sinensis-astragalus membranaceus exosomes, which comprises the following steps: firstly extracting exosomes in angelica sinensis and astragalus membranaceus, then adding the exosomes into an NK cell culture system according to a specific concentration, and regulating and controlling an NK cell signal channel by virtue of active ingredients carried by the exosomes so as to improve the proliferation and differentiation capacity of the NK cells. Therefore, the proliferation rate and differentiation maturity of the NK cells are remarkably improved. Experimental results show that compared with a traditional culture method, the proliferation multiple of the NK cells cultured through the method is increased by 28.99%-33.69%, the proportion of differentiated mature cells is increased by 15.91%-28.30%, and the cell killing activity is not remarkably reduced. The method can be widely applied to the field of immune cell treatment, provides a high-quality NK cell source for clinic, effectively solves the problems of slow cell proliferation rate, low differentiation maturity, easy activity reduction after large-scale culture and the like in traditional NK cell in-vitro culture, and has important clinical application value and industrialization prospect.

MUC1 binding molecules are provided, including MUC1 single domain antibodies that specifically bind to the MUC1 extracellular region. The invention further relates to an anti-MUC1 single-domain antibody chimeric antigen receptor and application thereof, and particularly provides the chimeric antigen receptor, and an antigen binding domain of the chimeric antigen receptor comprises an MUC1 binding molecule containing the anti-MUC1 single-domain antibody. The immune cell containing the chimeric antigen receptor has a relatively high cell killing effect.

The invention relates to the field of drugs, in particular to a linker drug conjugate, an antibody drug conjugate, and a preparation method and application thereof. Specifically, the invention relates to a connexon drug conjugate, or a pharmaceutically acceptable salt, solvate or solvate of the salt, the connexon drug conjugate has a structure as shown in formula I, M is a chemical structure containing a maleimide (m) fragment or a cyclooctyne fragment, x is a connecting fragment composed of 1-5 amino acids or derivatives thereof, and D is cytotoxin. The linker drug conjugate disclosed by the invention can release Payload through an enzymolysis reaction under the condition that a hydrophobic structure PAB is removed, so that the hydrophobicity of Linker-Rug can be reduced, the content of a polymer generated during preparation of ADC can be reduced, and corresponding cell killing activity (M-X-D formula I) can also be shown.

The disclosure belongs to the technical field of medicine. Provided are a CD97 and GSDME interaction inhibitor having anti-tumor activity and an application thereof. A compound screened in the disclosure enhances the susceptibility of NK cells to kill tumor cells by inhibiting the interaction between GSDME and CD97 in tumor cells, so as to induce an immune anti-tumor effect. Moreover, the compound enhances the susceptibility of tumor cells to pyroptosis by blocking the protective effect of CD97 on cleavage of GSDME proteins. Therefore, the compound can be used for treating GSDME and CD97 double-positive malignant tumors, and combined chemotherapy, immunotherapy, etc., to enhance the susceptibility of malignant tumors to chemotherapy and immunotherapy, prolonging the overall survival period of patients with malignant tumors. Specifically provided is a compound having a structure set forth in formula (I), a pharmaceutically acceptable salt, a solvent compound or a deuterated compound thereof.

The invention relates to the field of biological medicine, in particular to application of NPEPL1-targeted small molecule compounds in preparation of tumor targeted therapy drugs, and four small molecule compounds, namely C301-9181, E859-1332, L281-0443 and C679-2629, which have a hepatocellular carcinoma cell killing effect and high NPEPL1 affinity are obtained for the first time. The small molecule compound realizes tumor targeted therapy by targeting NPEPL1 protein in tumor cells, and can be used for developing tumor targeted therapy drugs. According to the present invention, the potential treatment effect of the targeted intervention NPEPL1 on hepatocellular carcinoma and other malignant solid tumors with high NPEPL1 expression is provided, the optimal small molecule compound C301-9181 is obtained through layer-by-layer screening, the small molecule compound can be used for preparing the NPEPL1-targeting anti-tumor targeting drugs, the drug research and development blank in the NPEPL1 targeting treatment field is filled, and the broad application prospect is provided.

The application discloses a nano-antibody (also known as single-domain antibody) conjugated photosensitizer targeting HER2, a preparation method of the photosensitizer and application of the photosensitizer in tumor photodynamic therapy. The photosensitizer is shown in a general formula (I). In the photosensitizer, the nano-antibody (N HER2 ) serving as a targeting ligand is connected with a photosensitive moiety (PS) through a catalytic reaction mediated by a transglutaminase (MTGase). Research finds that the anti-HER2 nano-antibody conjugated photosensitizer molecule has good cell killing selectivity and tumor enrichment capacity, and can remove a subcutaneous tumor of a mouse with high HER2 expression in one administration. HER2 -PEG 1K -PS (I).

The present invention relates to the identification of key residues within mouse IgG3 antibodies (mAbs) that are responsible for intermolecular cooperativity and their transfer into IgG1 antibodies in order to enhance their functional affinity and direct a cell killing.

The invention discloses a drug-loaded nanoparticle as well as a preparation method and application thereof. The drug-loaded nanoparticles comprise active components and a carrier, wherein the active components comprise a hydrophobic small-molecule inhibitor and PAEMA; the carrier comprises an amphiphilic polymer bonded with a photosensitizer; the amphiphilic polymer bonded with the photosensitizer is coated with a hydrophobic small-molecule inhibitor and PAEMA (Polyacrylamide); wherein the amphiphilic polymer bonded with the photosensitizer comprises the photosensitizer, a hydrophilic chain segment and a hydrophobic chain segment. Precise drug delivery is achieved through characteristic transformation of the nano-carrier driven by tumor acidity, M2 type macrophages can be removed, dendritic cells can be induced to be mature, tumor cells can be killed, and therefore the synergistic anti-tumor effect of photodynamic therapy and immunotherapy is enhanced. Therefore, various drugs can be accurately delivered to target cells with different spatial distributions, so that the cell killing level and the antigen presenting cell mediated immunocompetence are enhanced at the same time.

Provided is a bispecific antibody targeting a CD3 molecule and a tumor associated antigen (TAA) HER2, comprising a first binding domain targeting the CD3 molecule and a second binding domain targeting HER2, wherein the first binding 5-domain only binds to an epsilon(ε) subunit in a delta(δ)-epsilon(ε) heterodimer of the CD3 molecule, and does not bind to an epsilon(ε) subunit in a gamma(γ)-epsilon(ε) heterodimer of the CD3 molecule. The antibody has the activity of activating immune cells and triggering relatively less cytokine release, recruits T cells, and achieves a cell killing effect.

The invention relates to the technical field of biological medicines, and particularly discloses a nanocapsule SMCPM and application thereof in medicines for treating or preventing osteosarcoma and pulmonary metastasis. The SMCPM is composed of a photosensitizer Ce6 carried by mesoporous silicon oxide-manganese oxide particles, an NRF2 inhibitor ML385 and an OS targeting peptide PT-7. Experiments prove that the SMCPM is high in penetrating power and strong in cell killing effect; by down-regulating NRF2 expression and reversing nuclear translocation, a biochemical inhibitory microenvironment can be effectively repaired, the tolerance of cells to active oxygen and epithelial-mesenchymal transition activated and induced by a NOTCH1 signal axis are remarkably reduced, the oxidative stress level of the cells is enhanced, and PIT-induced immunogenic cell death is promoted; the released Mn < 2 + > and double-stranded DNA can regulate and control an immunosuppressive microenvironment by activating an STING pathway in cells, thereby inhibiting the growth of osteosarcoma and preventing lung metastasis.

The invention relates to recombinant human lysozyme with broad-spectrum tumor cell killing activity and application of the recombinant human lysozyme. Specifically, the invention discloses a novel application of recombinant human lysozyme (ghLZ), and the recombinant human lysozyme is completely consistent with natural human lysozyme and does not have any variant. The ghLZ not only retains the broad bactericidal activity of gram-positive bacteria of natural human lysozyme, but also has unique broad-spectrum in-vitro tumor cell killing activity.

The present application relates to the technical field of nucleic acid drug preparation, and discloses a lipid nanoparticle based on asiatic acid and a preparation method and application thereof, the lipid nanoparticle is composed of ionizable cationic lipids, structural lipids, neutral lipids, PEG lipids and asiatic acid with a molar ratio of 10-85:20-60:1-30:0.1-10:0.1-50, and is used as a delivery carrier of nucleic acid drugs for delivering nucleic acid drugs. The present application innovatively uses natural product asiatic acid to partially replace the structural lipids (such as cholesterol) in the traditional LNP formula, significantly optimizes the micro morphology, and greatly enhances the transfection and expression efficiency of mRNA in vitro and in vivo. The mRNA vaccine based on the carrier can induce the body to produce high-titer specific antibodies and significantly enhance the cytotoxic T lymphocyte (CTL) killing activity. The LNP system performs outstandingly in the field of tumor immunoprevention and treatment, and shows superior conversion application potential and broad market prospects.

The application belongs to the technical field of biological medicine, and particularly relates to application of a KAT5 inhibitor in a medicine for enhancing the immunotherapy effect of natural killer cells, and a medicine for enhancing the immunotherapy effect of natural killer cells. The KAT5 inhibitor comprises at least one of Nu9056, TH1834 and MG149. The KAT5 inhibitor can inhibit the recruitment of a transcription factor SP1 to an ADAM10 promoter, reduce the transcriptional activity of ADAM10, reduce the expression of NKG2D ligands on the cell surface, and thus enhance the sensitivity of tumor cells to NK cell killing. The application first discloses a new mechanism in which KAT5 regulates an ADAM10-NKG2D signal axis through an epigenetic mechanism, and proves that the KAT5 inhibitor can significantly enhance the immunotherapy effect of NK cells in vitro and in vivo. The application provides a brand-new target and strategy for developing a new immunosensitizer and a combined cell therapy.

Provided are multispecific B7H3-targeting compounds and methods of using the same. The multispecific compounds include bispecific targeting proteins comprising a B7H3-targeting domain and an immune cell engaging domain, and trispecific targeting proteins comprising a B7H3-targeting domain, an immune cell engaging domain, and an immune cell activating domain. The methods of using include methods of inducing NK-mediated cell killing, methods of inducing NK in vivo expansion, and methods of treating cancer.

Disclosed herein is an anti-tumor pharmaceutical composition based on immune checkpoint blockade and use thereof. The anti-tumor pharmaceutical composition comprises: paroxetine hydrochloride, and a T-cell enhancer, wherein the T-cell enhancer is at least one of vitamin E and thymosin. Through a series of in vitro and in vivo experiments, cannabidiol and paroxetine hydrochloride were first found to be capable of effectively reducing the expression of PD-L1 on the tumor cell membrane, thereby blocking the PD-1 / PD-L1 signaling pathway and enhancing the ability of T cells to kill tumor cells. The T-cell enhancer added on this basis can further increase the quantity and activity of T cells, significantly increase the killing ability of T cells after immunosuppression is relieved, and greatly improve the anti-tumor effect of the drug. The components of the pharmaceutical composition used in the present invention, namely, cannabidiol, paroxetine hydrochloride, and vitamin E+thymosin, can exert a synergistic effect and improve the anti-tumor effect.

Provided are a C9-substituted camptothecin derivative and a conjugate thereof. Specifically disclosed is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The camptothecin derivative and the conjugate thereof have a good cell killing effect.

The application discloses a CAR-NK cell based on a dendritic molecule and a preparation method and application thereof. The CAR-NK cell is an assembly formed by the dendritic molecule, effectively loads nucleic acid expressing CAR through electrostatic interaction, forms a stable and uniform delivery system with nanometer size, is safely and effectively delivered to NK cells by virtue of the dendritic molecule, and prepares the CAR-NK cell with high-efficiency target gene expression, so as to solve the problems of low NK cell transduction efficiency and safety of a virus vector and improve the curative effect of the CAR-NK cell. The use of the dendritic molecule for transfection does not affect the phenotype of the NK cell and surface activation and inhibition receptors thereof. The CAR-NK cell prepared based on the dendritic molecule has a remarkable target cell killing efficiency in vitro and a remarkable anti-tumor (Raji-Luc transplanted tumor model) effect in vivo.

The present application relates to signal conversion receptors, and specifically provides a signal conversion receptor comprising an extracellular region, a transmembrane region and an intracellular region, wherein the intracellular region comprises a CD25 intracellular domain, and optionally further comprises an intracellular domain of a costimulatory signaling molecule. An immune effector cell expressing the signal conversion receptor has a higher positive rate, activation level and target cell killing ability compared with a control cell.

The invention provides a camptothecin derivative and an antibody-drug conjugate thereof. The compound is high in activity, small in toxicity and good in affinity, the direct targeted killing effect on tumor cells is achieved through the compound and an antibody drug conjugate, and the antibody drug conjugate containing the antibody is remarkable in cell killing effect and has the very high tumor inhibition rate.

The invention relates to the technical field of biological medicine, in particular to an anti-B7H3 and CD3 bispecific antibody and application thereof. Aiming at the problem of lack of a bispecific antibody which simultaneously targets B7H3 and CD3 and can guide to kill tumor cells in the prior art, the invention provides the bispecific antibody for resisting B7H3 and CD3, and the bispecific antibody for resisting B7H3 and CD3 can be simultaneously combined with B7H3 and CD3 and can effectively mediate T cells expressing CD3 to kill cells expressing B7H3. According to the invention, the nano antibody targeting B7H3 and the anti-CD3 antibody OKT3 are constructed into the heterodimeric bispecific antibody, and the heterodimeric bispecific antibody still keeps good antigen binding activity; the prepared bispecific antibody has strong killing activity on B7H3 positive small cell lung cancer cells, effectively improves the treatment effect, and provides a key material for subsequent development of immunotherapy with efficient and lasting antitumor activity.

Engineered pH-dependent anti-CD3 binding domains and antibodies and / or antigen-binding domains comprising same, including multispecific antibodies, with, inter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use.

The present application provides an anti-CDH17 antibody or an antigen binding fragment thereof, which can be a bispecific antibody constructed. The anti-CDH17 antibody provided by the present application can specifically bind to CDH17 protein, has a relatively strong CDH17-expressing tumor cell killing effect, can be effectively internalized on CDH17-expressing tumor cells, and can be prepared into an ADC which can be effectively internalized on CDH17-expressing tumor cells and has high killing activity; in particular, compared with an antibody binding to a single epitope of CDH17, the bispecific antibody of the present application has more accurate and multi-dimensional antigen recognition ability and higher targeting.

The application discloses a near-infrared heptamethine cyanine dye and application thereof in the field of photothermal therapy. 2000 After being wrapped into nanoparticles, the photothermal stability of the heptamethine cyanine dye is greatly enhanced, no photobleaching occurs in four photothermal cycle experiments, the heptamethine cyanine dye has high efficient photothermal conversion capacity, and the photothermal conversion efficiency is as high as 82%. The photothermal reagent prepared from the heptamethine cyanine dye has significant cell killing capacity at low concentration and low light dose under light excitation, and has low dark toxicity. The near-infrared heptamethine cyanine dye provided by the application has simple structure, simple synthesis mode and excellent clinical application potential.

This utility model discloses a temporary storage device for detecting NK cell killing activity, relating to the technical field of temporary storage devices. The utility model includes: a storage tank, with a servo motor at the bottom end of the storage tank, and a drive shaft extending into one end of the storage tank from the output shaft of the servo motor. A support cylinder is fixedly sleeved on the drive shaft. This utility model involves placing a culture dish on a placement tray, then pouring liquid nitrogen into the storage tank, screwing on the tank lid, and turning on the servo motor to drive the drive shaft, which in turn rotates the support cylinder and fan blades. When the fan blades rotate, they drive air through the support cylinder to the outside of the support cylinder, forming a stable vertical circulation channel between the support cylinder and the inner wall of the storage tank. This facilitates the circulation of the cold liquid nitrogen to all parts of the storage tank, improving the temperature uniformity within the storage tank and the uniform cooling of the culture dish. When the support cylinder rotates, it causes the placement tray to engage with an internal toothed ring, rotating the placement tray and, consequently, the culture dish.

The application discloses a human head and neck squamous cell carcinoma clinical diagnosis reagent, which is a reagent for detecting the expression amount of a human NCAPH gene. The expression level of the human NCAPH gene is negatively correlated with the clinical prognosis of human head and neck squamous cell carcinoma. Experimental results show that the expression of the human NCAPH gene in a human head and neck squamous cell carcinoma cell line is higher than that in normal nasopharyngeal epithelial cells. Knocking down the expression of the human NCAPH gene can significantly inhibit the proliferation and colony sphere formation ability of the head and neck squamous cell carcinoma cells. The application also provides a drug for inhibiting the expression of the human NCAPH gene or a NPIDP small peptide drug for inhibiting the expression of the human PD-L1 gene. The NPIDP small peptide drug is used on human head and neck squamous cell carcinoma cells, can significantly compete to block the combination of NCAPH and HIP1R, promote the degradation of the PD-L1 protein, and thus enhance the T cell killing effect. The application provides a new diagnosis and treatment drug for the treatment of human head and neck squamous cell carcinoma.

Disclosed herein is an anti-tumor pharmaceutical composition based on immune checkpoint blockade and use thereof. The anti-tumor pharmaceutical composition comprises: paroxetine hydrochloride, and a T-cell enhancer, wherein the T-cell enhancer is at least one of vitamin E and thymosin. Through a series of in vitro and in vivo experiments, cannabidiol and paroxetine hydrochloride were first found to be capable of effectively reducing the expression of PD-L1 on the tumor cell membrane, thereby blocking the PD-1 / PD-L1 signaling pathway and enhancing the ability of T cells to kill tumor cells. The T-cell enhancer added on this basis can further increase the quantity and activity of T cells, significantly increase the killing ability of T cells after immunosuppression is relieved, and greatly improve the anti-tumor effect of the drug. The components of the pharmaceutical composition used in the present invention, namely, cannabidiol, paroxetine hydrochloride, and vitamin E+thymosin, can exert a synergistic effect and improve the anti-tumor effect.

The invention relates to the technical field of engineering antibodies, in particular to an antibody combined with TROP2, a bispecific antibody targeting TROP2 and CD3 as well as a preparation method and application of the bispecific antibody. According to the present invention, the TROP2 antibody has good TROP2 binding ability, and has high affinity; the bispecific antibody combined with the TROP2 and the CD3 has excellent biological functions of anti-TROP2 and anti-CD3 antibodies, a bridge can be built between tumor cells and immune effector cells, the immune effector cells and oriented immune response are effectively activated, the tumor cell killing effect of the immune cells is remarkably enhanced, meanwhile, the ADCC effect is reduced to the maximum extent, and the tumor cell killing effect is improved. The compound has high safety and has a good application prospect in immunotherapy of tumors.

The invention discloses an NK cell killing resistant cell strain as well as a construction method and application thereof. The NK cell killing resistant cell strain is named as a human liver cancer cell HepG2-NK-R Homo sapiens, and is preserved in the China Center for Type Culture Collection on November 05, 2025, and the preservation number is CCTCC (China Center for Type Culture Collection) NO: C2025298. The human hepatoma cell line HepG2 is exposed to NK cells for a long time for co-culture to obtain the human hepatoma cell line HepG2. The cell strain has a stable biological phenotype through in-vitro simulation of NK cell mediated long-term immune editing. Compared with parental cells, the cell line shows remarkably enhanced malignant biological behaviors, can be used for researching occurrence, development and metastasis of liver cancer or preparing a tumor cell model or a tumor animal model, is greatly improved in tumor forming ability, in-vivo proliferation speed and metastasis speed, can remarkably shorten an experimental period, and can highly restore invasion characteristics of tumors after evolution.

The present invention relates to a novel unconventional method of cell killing for selectively killing or / and inhibiting the growth of target cells. This unconventional method is to kill target cells by persistently over-accumulating organelle-localization sequence fusion antibodies (OLS fusion antibodies) in a key organelle of the target cells with the purpose of clogging or over-occupying the key organelle. The OLS fusion antibodies comprise a cell-binding domain and an organelle-localization sequence (OLS) without any cytotoxic payload. The cell-binding domain of the OLS fusion antibodies functions to selectively bind to a cell-surface antigen of the target cells. The OLS fragment of the OLS fusion antibodies functions to direct the OLS fusion antibodies to a specific organelle of the target cells. The present invention first demonstrates that selectively and persistently accumulating OLS fusion antibodies in a key organelle of the target cells can kill or / and inhibit the growth of the target cells.