38 results about "Cell tumor" patented technology

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The invention relates to the field of biological medicine, and discloses application of a GADD34 inhibitor in preparation of a medicine for enhancing CAR-T cell tumor treatment. The invention provides an innovative strategy for inhibiting CAR-T cell depletion through targeted regulation and control of an endoplasmic reticulum stress pathway to solve the problems that in an existing CAR-T therapy, the anti-tumor activity is reduced, and the solid tumor treatment effect is insufficient due to T cell depletion. Researches find that an IRE1-XBP1 pathway is used as a core signal axis of endoplasmic reticulum stress, and excessive activation of the IRE1-XBP1 pathway can drive CAR-T cell depletion related phenotypes (such as PD-1 / LAG-3 up regulation and cytokine secretion reduction). Screening experiments show that inhibiting the upstream regulatory factor GADD34 of the IRE1 not only can effectively reduce the IRE1-XBP1 signal intensity, but also can cooperatively relieve the endoplasmic reticulum stress pressure by regulating protein translation recovery, so that the CAR-T cell steady state is more comprehensively maintained. Therefore, the GADD34 inhibitor can provide a new way for enhancing CAR-T cell tumor treatment.

Systems and methods for identifying a diagnosis of a cancerous state for a somatic tumor specimen of a subject are provided.SOLUTION: The method receives sequencing information comprising an analysis of a plurality of nucleic acids from a somatic tumor specimen. The method identifies a plurality of features from the sequencing information including two or more of RNA, DNA, RNA splicing, viral, and copy number features. The method provides a first subset of features and a second subset of features from the identified plurality of features as input to a first classifier and a second classifier, respectively. The method generates two or more predictions of cancer status based at least in part on the identified plurality of features from the two or more classifiers. The method combines the two or more predictions with a final classifier to identify a diagnosis of cancer status for the subject's somatic tumor specimen.SELECTED DRAWING: Figure 1

The invention provides an application of 2-indolecarboxylic acid in preparation of a tumor targeted therapy drug. Through computer-aided drug design and molecular docking optimization, 2-indolecarboxylic acid shows high binding energy to an HER2 kinase structural domain. In HER2 positive NCI-N87 gastric cancer cells, the 2-indolecarboxylic acid significantly inhibits cell proliferation and induces G0 / G1 phase arrest and apoptosis. The mechanism research shows that the 2-indoleformic acid can play a role by regulating and controlling the HER2 / Akt / beta-catenin pathway (Western blot verification). In an NCI-N87 cell tumor-bearing nude mouse model, 2-indolecarboxylic acid (15 mg / kg) significantly inhibits tumor growth, and does not cause obvious weight loss or organ toxicity. Immunohistochemical analysis shows that the positive rate of a tumor tissue proliferation marker Ki-67 in a treatment group is remarkably reduced, and apoptosis detection shows that the proportion of TUNEL positive cells is remarkably increased, which indicates that 2-indolecarboxylic acid inhibits tumor cell proliferation and promotes apoptosis at the same time. The invention provides a lead compound with clinical transformation potential for HER2 targeted therapy.

The invention belongs to the technical field of biomedical treatment, and particularly relates to application of an ACA49 overexpression reagent and / or an SOX9 expression inhibitor in preparation of a medicine for treating liver cancer. Experimental verification shows that when the ACA49 overexpression reagent and / or the SOX9 expression inhibitor is injected into a liver cancer cell tumor mouse, the quantity of liver cancer tumor cells of the mouse and the growth of the tumor can be remarkably inhibited, and the ACA49 overexpression reagent and / or the SOX9 expression inhibitor have no obvious influence on visceral organs of the mouse and are high in safety.

The invention discloses a method for evaluating activity of a single CTC through deep learning based on nucleus morphology. The method comprises the following steps: acquiring cell nucleus images of CTCs in different vitality states through a fluorescence inverted microscope, constructing five state data sets of the cell nucleus by utilizing Cellpose3.0 and ImageJ, realizing accurate positioning and classification by combining an improved YOLOv8x model, and calculating a single cell vitality value by adopting transfer learning and confidence coefficient weighting. The method has the advantages of no label, no toxicity and single-cell-level resolution, solves the problems of group signal dependence, phototoxicity interference and low sensitivity of a traditional method, and provides a new tool for tumor metastasis monitoring and individualized treatment.

This invention discloses an arginine-glycine-aspartic acid (RGD) peptide-modified chiral atomically precise metal nanoclusters, their preparation, and applications. The RGD peptide-modified chiral atomically precise metal nanoclusters consist of an atomically precise metal core, a chiral RGD peptide ligand layer, and linking molecules connecting the metal core and ligand layer. The chiral regulation and targeting functions of the RGD peptide-modified chiral atomically precise metal nanoclusters synergistically enhance their targeting and penetration at the tissue and cellular levels, thereby improving their uptake efficiency. After optimization with α... v The binding constant of β3 integrin is 1.4 × 10⁻⁶. ‑6 M ‑1 RGD peptides modify the ultrasmall metal cores of chiral atomically precise metal nanoclusters, endowing them with highly efficient and rapid renal clearance properties. This invention provides a solution suitable for various α-cell tumors, arthritis, liver fibrosis, and other conditions. v RGD peptides modified with chiral atomic precision metal nanoclusters, used to treat diseases with high expression of β3 integrin, can achieve efficient enrichment at target sites for imaging.

The invention belongs to the technical field of biological medicine, and relates to a three-specificity adapter for enhancing the anti-tumor function of T cells and application of the three-specificity adapter. An immunoregulation module, a T cell recognition module and a tumor cell recognition module form a multi-section structure through a first connector and a second connector; the immunoregulation module is connected with the T cell recognition module through a first connector, and the T cell recognition module is connected with the tumor cell recognition module through a second connector; the amino acid sequence of the first connexon is as shown in SEQ ID NO: 4, and the amino acid sequence of the second connexon is as shown in SEQ ID NO: 5. The three-specificity adapter provided by the invention can simultaneously promote mTLS formation and T cell anti-tumor immune response, accurately regulate and synergistically improve the T cell tumor killing effect, and further improve the disease treatment effect.

It is an object of the present invention to provide a therapeutic agent for NK-cell tumor. According to the present invention, a therapeutic agent for NK-cell tumor, which comprises a substance that recognizes a transferrin receptor, is provided.

The present invention provides a CAR-T cell production method and application thereof, which belongs to the field of tumor immunotherapy technology. The present invention first prepares CAR-T cells that overexpress Runx3, and then amplifies the CAR-T cells that overexpress Runx3 in a 1μM AKTi1 / 2 environment, thereby producing a new type of CAR-T cell. Wherein Runx3 overexpression can enhance the effector function of CAR-T cells and promote CAR-T cell tumor infiltration, but does not affect the maintenance of T cell stemness that depends on AKT inhibitors. The use of AKT inhibitors can save the problem of CAR-T cells not being able to survive continuously and amplify insufficiently in vivo. The two work together and complement each other, so the new CAR-T cells produced have better long-term survival, effect and solid tumor infiltration capabilities, and thus have a stronger comprehensive ability to overcome the dilemma of solid tumors.

This invention discloses a panel for detecting histiocytic / dendritic cell tumors based on 10-color multiparameter flow cytometry and its applications. The panel is composed of the following antibodies: CD4, HLA-DR, CD45, CD1c, CD207, CD123, CD56, CD1a, CD3, and CD14. The flow cytometry protocol provided by this invention enables rapid, objective, and quantitative analysis of large numbers of cells, and is particularly suitable for detecting small tumor populations in mixed cell populations or assessing the heterogeneity of antigen expression. This is an important supplement to existing pathological diagnostic systems and provides key evidence for precision medicine.

This invention provides a nucleic acid aptamer that targets and binds to the IGF2BP2 protein and its application, belonging to the field of pharmaceutical technology. This invention is the first to design a highly specific nucleic acid aptamer targeting the RNA recognition protein IGF2BP2, obtaining a nucleic acid aptamer that can target and specifically bind to the IGF2BP2 protein (see SEQ ID No. 1-2). This nucleic acid aptamer can effectively inhibit the activity of tumor cells, tumor stem cells, and breast cancer brain metastases, breast cancer lung metastases, breast cancer liver metastases, breast cancer kidney metastases, and breast cancer bone metastases, providing a new drug component for the treatment of malignant and refractory tumors (especially glioblastoma and distant metastatic breast cancer). Furthermore, it was discovered that modification with N6-methyldeoxyadenosine monophosphate can further enhance the specificity of the nucleic acid aptamer and strengthen its efficacy in inhibiting tumor cell activity.

The invention relates to a 7-ethyl-10-hydroxycamptothecin polymer which has a structural formula as shown in (I), R is S or S-S, m is an integer selected from 20-200, and n is an integer selected from 2-40. The 7-ethyl-10-hydroxycamptothecine SN38 is subjected to structural modification by using beta-CD-PEG, and an-S-or-S-S-ligand with a redox function is used as a connecting arm to prepare the amphiphilic polymer-drug conjugate beta-CD-PEG-R-SN38, so that the water solubility and the stability of the SN38 are improved; meanwhile, the beta-CD-PEG-R-SN38 is prepared into self-assembled nanoparticles, and the self-assembled nanoparticles are high in drug loading capacity, moderate in particle size, uniform in dispersion, low in toxicity and good in biocompatibility, and show an obvious tumor growth inhibition effect in cell tumor-bearing nude mouse models of H22 liver cancer, 4T1 mouse breast cancer, SW480 colon cancer, KB oral epidermal cancer and the like.

The application discloses a chimeric antigen receptor targeting human CD47, macrophages expressing the chimeric antigen receptor and application of the chimeric antigen receptor and the macrophages. The specific structure of the chimeric antigen receptor targeting human CD47 is anti-CD47(scFv)-CD8-4-1BB-CD3zeta. The chimeric antigen receptor is transferred into the macrophages by the adenovirus infection mode, and the macrophages are endowed with the ability of specifically recognizing CD47 antigens and killing CD47 overexpressing tumor cells. The application is a new emerging adoptive cell tumor immunotherapy, and the killing effect on tumor cells is obvious, thereby providing a new selection for the field.

The invention discloses an application of aminooxyacetic acid in combination with an STING agonist in enhancing tumor immunity and treating colorectal cancer. Experiments prove that the combination of aminooxyacetic acid and STING agonist (such as cGAMP) can significantly inhibit tumor growth and prolong the lifetime of tumor-bearing mice in a subcutaneous transplantation tumor mouse model established by a colorectal cancer cell line MC38 for the first time. An in-vivo experiment verifies that the tumor volume is obviously reduced compared with that of a control group after aminooxyacetic acid and cGAMP are combined for treatment, and the median lifetime of a tumor-bearing mouse is obviously prolonged; further experiments show that the combination of the aminooxyacetic acid and the STING agonist can activate the tumor immune microenvironment, specifically, more CD8 + T cell tumor microenvironment infiltration is shown, and the CD8 + T cells have stronger functional effects.

Described herein are methods and compositions for treating solid or liquid B-cell malignancies using a two-component platform based on morpholino oligonucleotide-linked conjugates to target B-cells and effector cells. The methods described herein may involve two distinct dosing approaches tailored to the type of B-cell malignancy being treated. In some embodiments, solid B-cell tumors are treated using a premixed assembly dosing regimen. In some embodiments, liquid B-cell tumors are treated using a consecutive dosing regimen.

The invention provides a PD-L1 targeting compound HF12 as well as a preparation method and application thereof, and relates to the technical field of medicine synthesis. The radioactive probe [68Ga] Ga-HF12 provided by the invention has the biological characteristic of specifically targeting PD-L1, the uptake level of PD-L1 positive cells is high, the affinity is good, the SUV value of tumors of PD-L1 positive cell tumor-bearing mice in PET (Polyethylene Terephthalate) imaging is high, and the radioactive probe [68Ga] Ga-HF12 can be used for early diagnosis and pathological research of PD-L1 high-expression tumors and can be used for clinical application. Disease course development and curative effect evaluation are evaluated.

A CD19-targeting CAR-gdT cell and a use thereof in B-cell tumors and autoimmune diseases. Specifically, the human CD19-targeting CAR-gdT cell comprises CD19-targeting scFv, a CD28 costimulatory signaling molecule, a CD3ζ domain, and exogenous IL-2 required for sustained gdT proliferation. In-vitro and in-vivo experiments show that the CAR-gdT cell exhibits significant specific killing of CD19-positive (CD19+) tumor cell strains, and no gdT cells with tumor-promoting properties emerge. The CD19-targeting CAR-gdT cell can be used as an allogeneic off-the-shelf therapy for targeting CD19+ tumor cells, and can also be used for treating autoimmune diseases caused by B cell hyperactivation.

The invention discloses an application of combination of aminooxyacetic acid and a chemotherapeutic drug gemcitabine in enhancing tumor immunity and treating colorectal cancer. Experiments prove that the combination of aminooxyacetic acid and gemcitabine can significantly inhibit tumor growth and prolong the lifetime of tumor-bearing mice in a subcutaneous transplantation tumor mouse model established by a colorectal cancer cell line MC38 for the first time. In-vivo experiments prove that the tumor volume after treatment by combining aminooxyacetic acid with gemcitabine is remarkably reduced compared with that of a control group, and the median lifetime of tumor-bearing mice is remarkably prolonged; further experiments show that the combination of the aminooxyacetic acid and the gemcitabine can activate the tumor immune microenvironment, specifically, more CD8 + T cell tumor microenvironment infiltration is shown, and the CD8 + T cells have stronger functional effects.

The present application relates to a kind of polypeptides, and specifically relates to a kind of tumor targeting peptide and its application;Tumor targeting peptide p46-2 is the carboxyl end of the 361-382 fragment of human cell tumor antigen p53 by connecting peptide and tumor targeting fragment arginine-glycine-aspartic acid-arginine connection;Chemotherapy drugs include paclitaxel, epirubicin, 5 fluorouracil;Selected tumor types include breast cancer, colorectal cancer.Tumor targeting polypeptide and classic chemotherapy drug combination therapy tumor, can obviously achieve the effect of drug synergism.

The application relates to the field of biological medicine, and relates to a method for enhancing the tumor killing effect of NK cells and application, in particular to a method and application of fraxidin in enhancing the tumor killing effect of NK cells; through experiment verification, it is proved that the fraxidin can improve the killing ability of NK cells to tumor cells under the hypoxic tumor microenvironment, and up-regulate the expression of active molecules on the surface of NK cells and NK cell activation receptors; the fraxidin is used to regulate the NK activity for the first time, and the method has important significance.

Aspects of this invention are related to the use of N-desmethyl ruboxistaurin and pharmaceutically acceptable formulations thereof to modulate CDK4 / 6 signaling. The invention encompasses methods for administering N-desmethyl ruboxistaurin to subjects in need, particularly those with a history of cancer or currently experiencing breast cancer, liposarcoma, lung cancer, glioblastoma, melanoma, pancreatic cancer, prostate cancer, colon cancer, ovarian cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma, osteosarcoma, germ cell tumors, advanced solid tumors, lymphoma, leukemia and other hematologic malignancies. The disclosed methods extend beyond disease treatment, including supportive care during radiation chemotherapy and prevention of cancer relapse. N-desmethyl ruboxistaurin administration, alone or in combination with other cancer therapies, is effective in modulating CDK4 / 6 signaling while mitigating toxicity associated with other treatments.

The invention relates to the technical field of biological medicines, and particularly provides a preparation method of an engineered bispecific nano antibody and application of the engineered bispecific nano antibody in treatment of lymphoma. The engineered bispecific nano-antibody provided by the invention is prepared by taking silicon dioxide nano-particles as a main body and modifying a polyethylene glycol chain, an amino group, a carboxyl group and an antibody combination on the surface of the silicon dioxide nano-particles through a chemical reaction. According to the invention, an HSNP-alphaCD3 / alphaCD19 or HSNP-alphaCD3 / alphaCD20 engineered bispecific nano antibody is constructed by modifying an antibody targeting a T cell CD3 molecule and a tumor antigen CD19 / CD20 on the surface of HSNP, so that a T cell-tumor cell double-targeting synergistic activation effect is realized. The engineered bispecific nano antibody has excellent tissue permeability, long circulation half-life period and multi-antigen targeting capability, can effectively bridge tumor cells and T cells, activates T cell mediated cytotoxicity, and significantly improves the anti-tumor curative effect.

The invention discloses a tumor microenvironment exosome mixer based on a micro-fluidic chip, application and an operation method, and a micro-fluidic operation platform and an operation method for improving the balling rate of single-cell tumor balls. Different types of tumor microenvironment exosomes are mixed to simulate a tumor microenvironment in vitro, co-culture with single tumor cells with different sizes and deformability is carried out, and the influence of the tumor microenvironment exosomes on the biological activity of the tumor stem cells and the heterogeneity of the tumor stem cells are researched. Compared with a traditional method for constructing and simulating the tumor microenvironment by utilizing tumor microenvironment cells, the method disclosed by the invention is simple to operate and high in condition controllability, so that the method has good scientific research and clinical application prospects.

The invention belongs to the technical field of immunology and biological medicine, and relates to application of CD28 CAR in substances for simultaneously killing plasma cell tumors and T cell tumors. The invention relates to application of CD28 CAR in preparation of substances for killing plasma cell tumors and T cell tumors, in particular to application in preparation or screening of CAR-T products with high safety, and the amino acid sequence of the CD28 CAR protein is shown as SEQ ID NO: 1. The CD28 CAR-T cell can safely and efficiently kill plasma cell tumors and T cell tumors at the same time, shows good amplification capacity, and does not generate a cell suicide phenomenon. According to the CAR-T cell immunotherapy, the problem of sib suicide is expected to be reduced, the killing efficiency of CAR-T cells is improved, the release of inflammatory factors is reduced, synchronous removal of various tumors is realized, key barriers of the CAR-T therapy in tumor immunotherapy are expected to be overcome, and a new hope of'healing 'is provided for patients with hematologic tumors and even solid tumors.

The present invention relates, in part, to the use of dendritic cell-tumor fusion vaccines and a Bcl-2 inhibitor (e.g., venetoclax) to treat or prevent certain cancers.

This invention belongs to the interdisciplinary field of biomedicine and nanotechnology, specifically relating to a method and system for inactivating whole-cell vaccines targeting immunogenic cell death. The method includes: contacting tumor cells with magnetic nanoparticles and internalizing them into the cell; placing the system to be treated in an alternating magnetic field, achieving heating from the inside out through in-situ intracellular heat generation; monitoring the temperature in real time with a fixed sampling period; dynamically adjusting the magnetic field strength and / or frequency based on the deviation between the temperature and the target temperature range, causing the temperature to fluctuate within the immunogenic cell death induction window; accumulating the effective time, and stopping the magnetic field after reaching the preset inactivation time. This invention, through the spatiotemporal coupling of magnetic nanoparticle internalization, closed-loop feedback control, and the accumulated effective time strategy, actively induces immunogenic cell death while ensuring 100% inactivation, obtaining a highly immunogenic whole-cell tumor vaccine. This solves the technical problems of thermal hysteresis, thermal overshoot, and inability to accurately induce immunogenic cell death in traditional thermal inactivation methods.

The present disclosure is concerned with substituted quinazoline-2,4-diamines and compositions for the treatment of disorders associated with altered expression of SMARCA2 and / or SMARCA4 such as, for example, cancer (e.g., sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, gliomas, leukemia, lymphoma, chronic myeloproliferative disorders, myelodysplastic syndrome, myeloproliferative neoplasm, non-small cell lung carcinoma, plasma cell neoplasm (myeloma)). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The described invention provides a tumor cell vaccine comprising genetically modified tumor cell line of a particular tumor type that stably expresses high levels of two or more immunomodulators. According to some embodiments, an immunogenic amount of the tumor cell line variants may be selected for concomitant expression of two or more of recombinant membrane expressed IgG1, CD40L, TNF-alpha, as well as membrane and soluble forms of GM-CSF, and Flt-3L peptides that are effective to elicit an anti-tumor immune response compared to the parent unmodified tumor cell line as measured in vitro by a one-way mixed lymphocyte tumor reaction assay using human peripheral blood mononuclear cells and the genetically modified allogeneic cell vaccine candidate. According to some embodiments, the tumor cell vaccine candidate will induce an immune response in the recipient cancer patient that cross reacts with the patient's own (autologous) tumor cells, the effects of which will be sufficient to result in enhanced anti-tumor immunity contributing to the increased survival of a vaccinated patient cohort compared to a matched unvaccinated patient cohort.

The invention provides a CAR-gdT cell targeting CD19 and an application of the CAR-gdT cell in B cell tumors and autoimmune diseases. Specifically, the CAR-gdT cell targeting the human CD19 disclosed by the invention comprises scFv targeting the CD19, a CD28 costimulatory signal molecule, a CD3 zeta structural domain and an exogenous IL-2 (Interleukin-2) required by continuous proliferation of the gdT. In-vitro and in-vivo experiments show that the CAR-gdT cell disclosed by the invention has obvious specific killing effect on CD19 positive CD19 + tumor cell strains, and no gdT cell with tumor promoting characteristic appears, so that the CAR-gdT cell has high safety. The CD19-CAR-gdT cell disclosed by the invention can be used as a novel allogenic universal therapy for targeting CD19 < + > tumor cells, and also provides a new strategy for treating autoimmune diseases caused by excessive activation of B cells.