119 results about "Human 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 belongs to the technical field of tumor vaccines, and particularly relates to an mRNA (messenger Ribonucleic Acid) vaccine for coding tumor antigen epitopes as well as a preparation method and application thereof. In order to overcome the defect of immune escape caused by insufficiency or loss of a single antigen, the invention provides an mRNA vaccine capable of simultaneously coding a plurality of tumor antigen epitopes, and the tumor antigen epitopes are selected from high-frequency mutation epitopes of human tumor driving genes, such as G12D, G12V and G12C mutations of RAS genes; the antigenic epitopes can be used for preparing antigenic epitopes related to common viruses of human tumors, such as HPV16E6 / E7, EBV LAMP1 or CMV pp65, and tumor high-expression carcino-embryonic antigen gene epitopes, such as MAGE-A4, NY-ESO-1, WT1, and the like. The mRNA vaccine is obtained by serially expressing a plurality of tumor antigen epitopes and encapsulating and delivering lipid nanoparticles. Experiments prove that the compound can effectively prevent and treat various tumors and has a wide application prospect.

The invention discloses a bispecific antibody which comprises a first protein functional region targeting CD30 and a second protein functional region targeting CD16a, the first protein functional region comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3. The invention also discloses nucleic acid for coding the antibody, a recombinant expression vector, a transformant, a preparation method of the antibody, an antibody drug conjugate, a pharmaceutical composition or a kit containing the antibody drug conjugate, and applications of the nucleic acid, the recombinant expression vector and the transformant in preparation of drugs for preventing and / or treating tumors. The bispecific antibody provided by the invention can effectively activate the NK cells and can effectively target human tumor cell related antigen CD30 protein, mediate the killing activity of the NK cells to target cells, and induce and further enhance the tumor inhibition effect of the NK cells to tumor cells.

The present invention provides an antibody binding a human tumor-associated calcium signal sensor 2 (Trop-2) protein or fragments thereof, and use of the antibody or fragments thereof in preventing or treating diseases. The antibody or fragments thereof of the present invention can effectively bind to the human Trop-2 protein, and have internalization activity, and the internalization activity is enhanced after ADC drug labeling, and the in vivo efficacy and safety of a mouse model are not lower than those of a control antibody.

A method and kit are provided for detecting anti-drug antibodies (ADAs) against self-assembling trimeric biologics, such as XPro1595, a pegylated variant of soluble human Tumor Necrosis Factor, in biological samples, particularly human serum. The method employs an Affinity Capture Elution-Protein A / G (ACE-AG) assay that overcomes non-specific reagent interactions inherent in conventional bridging and standard ACE assays due to the biologic's dynamic monomer exchange. The assay utilizes a two-plate system: a streptavidin-coated plate with biotinylated trimeric biologic captures ADAs, which are eluted, neutralized, and transferred to a protein A / G-coated plate for specific immunoglobulin capture and detection with a sulfo-tagged trimeric biologic via electrochemiluminescence. The kit includes pre-coated plates, labeled biologics, elution and neutralization solutions, assay buffer, confirmatory reagent, and instructions. The assay offers a robust, specific, and sensitive solution for immunogenicity testing of trimeric biologics.

The invention relates to a 5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound as well as a preparation method and medical application thereof. The compound is efficiently synthesized through Ullmann coupling and palladium-catalyzed intramolecular arylation reaction. In-vitro anti-tumor activity research shows that the compound has remarkable selective inhibitory activity on various human tumor cell lines, and particularly, the inhibitory effect on non-small cell lung cancer A549 cells (IC50 = 0.21 mu M) is improved by two orders of magnitude compared with that of cis-platinum; iC50 (half maximal inhibitory concentration) of other cell lines are as follows: 1.26 mu M of prostate cancer PC-3 cells, 6.78 mu M of liver cancer HepG2 cells, 7.99 mu M of cervical cancer Hela cells and 25.46 mu M of breast cancer MCF-7 cells. Preliminary toxicity experiments prove that the compound has the characteristic of low cytotoxicity. The compound can be used as a novel high-efficiency low-toxicity anti-tumor lead compound, and provides an important structural basis for the development of anti-cancer drugs.

The invention relates to the technical field of biology, in particular to an anti-LIV-1 antibody or an antigen binding fragment thereof, an antibody drug conjugate and application thereof. Specifically, the LIV-1 antibody obtained by the invention has higher affinity and good endocytosis rate; the antibody drug conjugate containing the antibody has a remarkable cell killing effect and has a very strong tumor growth inhibition effect. The invention also relates to application of the antibody or the antigen binding fragment thereof and the antibody drug conjugate in preparation of drugs for treating cancers, and the antibody or the antigen binding fragment thereof and the antibody drug conjugate play an important role in treatment of human tumors.

The invention belongs to the field of organic synthesis and medicinal chemistry, and particularly provides an efficient synthesis method of an N, N-diphenyl aniline compound based on a naphtho-indolizino-phenothiazine skeleton and anti-tumor application of the N, N-diphenyl aniline compound based on the naphtho-indolizino-phenothiazine skeleton. Through Suzuki reaction, functional coupling based on a naphtho-indolizino-phenothiazine skeleton and an N, N-diphenyl aniline group is realized for the first time. In-vitro anti-tumor evaluation shows that the compound has remarkable inhibitory activity on various human tumor cells, especially has the strongest effect on breast cancer MCF-7 cells (IC50 = 0.15 mu M), and the activity is improved by 266 times compared with that of cis-platinum; prostate cancer PC-3, liver cancer HepG2, lung adenocarcinoma A549 and cervical cancer Hela cells are also remarkably inhibited. The toxicity to normal umbilical vein endothelial cells (HUVEC) is far lower than that of tumor cells, and the selectivity is excellent. The research provides a lead compound with great potential for developing high-efficiency and low-toxicity targeted anti-tumor drugs.

The invention belongs to the technical field of biological medicine, and particularly relates to application of actinomycin D in preparation of a ctDNA detection sensitizer. The invention provides a ctDNA release method based on actinomycin D as an enhancer, which can significantly improve the release level of ctDNA in early small-volume tumors and tiny residual lesions, thereby improving the sensitivity and positive detection rate of liquid biopsy in MRD detection. Under an extremely low dosage, the ActD can generally promote a plurality of human tumor cells to release ctDNA under the condition of not causing obvious cell death, and has good biological safety and adaptability. The method is especially suitable for tiny, biological inert or anatomical position hidden focuses which are difficult to identify by iconography, namely blind area patient groups in disease monitoring, and has a wide clinical application prospect.

This invention discloses a class of pentacyclic triterpenoid derivatives with diverse B-ring modifications, their preparation methods, and applications. This invention utilizes a chemical enzymatic method to expand the chemical space of the B-ring in pentacyclic triterpenoids, obtaining a series of pentacyclic triterpenoid derivatives with diverse B-ring modifications. Pharmacological activity screening of these pentacyclic triterpenoid derivatives revealed their good tumor-suppressive activity, providing a promising application prospect for the prevention and treatment of tumors. This invention achieves the efficient synthesis of pentacyclic triterpenoid derivatives with diverse B-ring modifications, structures that are difficult to obtain using traditional chemical methods. Systematic antiproliferative activity screening identified candidate molecules with broad-spectrum and highly efficient inhibitory effects against various human tumor cell lines. These molecules show good drug development potential, providing novel lead compounds for the innovative development of anticancer drugs.

The application discloses a kind of thieno [2, 3-c] pyrazole compounds in preparation antitumor drug purposes, belong to pharmaceutical chemistry technical field.The application provides a kind of small molecule skeleton thieno [2, 3-c] pyrazole compound I and II, compound I is 2-oxo benzo [d] [1, 3] oxathiole-6-yl 1-(3-fluorophenyl)-3-methyl-1H-thieno [2, 3-c] pyrazole-5-carboxylate.Compound II is 1-(4-chlorophenyl)-N-[4-((4-ethylpiperazine-1-yl)methyl)phenyl]-3-methyl-1H-thieno [2, 3-c] pyrazole-5-formyl.Both have strong antitumor activity.Compound II has strong inhibition to a variety of human tumor cells, such as bone sarcoma MG63, breast cancer HCC1806, liver cancer LM3, lung cancer A549, colorectal cancer HCT-8 and the like, provides new candidate compounds for broad-spectrum antitumor drugs.

We provide antigen-based immunotherapy, particularly cancer immunotherapy. [Solution] The present invention provides antigenic peptides that are different from human tumor antigen epitopes but have amino acid similarities thereto, and in particular share the same core sequence. The present invention further provides immunogenic compounds, nanoparticles, cells, and pharmaceutical compositions comprising such antigenic peptides and nucleic acids encoding such antigenic peptides.

The present invention relates to antigen-based immunotherapy, in particular cancer immunotherapy. Specifically, the invention provides antigen peptides which are different from human tumor antigen fragments but have amino acid similarity. The invention further provides immunogenic compounds, nanoparticles, cells and pharmaceutical compositions comprising such antigen peptides as well as nucleic acids encoding such antigen peptides.

The invention belongs to the technical field of organic synthesis and medicinal chemistry, and particularly relates to a synthesis method and anti-tumor application of a novel polycyclic aromatic hydrocarbon derivative 2, 6-di-tert-butyl phenanthroindolizino phenothiazine compound. The synthesis process is simple and convenient, and the yield is ideal. Pharmacodynamic evaluation shows that the compound has remarkable selective inhibitory activity on various human tumor cells, and the IC50 values of the compound are respectively as follows: Helaa (0.1 [mu] M), PC-3 (0.43 [mu] M), HepG2 (11.38 [mu] M), A549 (1457 [mu] M) and MCF-7 (88.25 [mu] M). Compared with cis-platinum, the compound has the advantages that the inhibiting effect on MCF-7 is weak, the inhibiting activity on other tumor cell lines is remarkably enhanced, and particularly, the IC50 value on Hela and PC-3 cells is reduced by two orders of magnitude. The compound has excellent anti-tumor activity and relatively low cytotoxicity, and has a good prospect in research and development of anti-tumor drugs.

The invention relates to the technical field of medicines, in particular to an enantiomer-atesane type diterpenoid compound as well as a preparation method and an application of the enantiomer-atesane type diterpenoid compound. The enantiomer-atesane diterpenoid compound disclosed by the invention is derived from plants, has anti-tumor activity, has cytotoxicity to human leukemia cells, human liver cancer cells and human cervical cancer cells, and is relatively good in inhibitory activity. Wherein the compound 3 has the best effect, the IC50 values of the compound 3 to three human tumor cells are 7.5 + / -1.2 micromole per liter, 9.8 + / -1.0 micromole per liter and 10.1 + / -0.9 micromole per liter respectively, and the activity of the compound 3 is equivalent to that of a positive control drug mitomycin. Particularly, the compound 3 also has good cytotoxicity to drug-resistant liver cancer cells (Huh7-LR cells), and the IC50 value of the compound 3 is 9.6 + / -1.1 micromole per liter. The compound 3 shows huge potential as a lead compound by virtue of the novel chemical structure and potent cytotoxicity shown in various cell lines.

The application relates to the technical field of biological medicine, and discloses siRNA for inhibiting a P311 gene, a composition and application thereof. The siRNA can specifically knock down P311 gene expression in human tumor cells, can be used as an auxiliary component for improving the drug efficacy of gemcitabine, can improve the drug sensitivity of a pancreatic cancer patient to gemcitabine, can reduce the gemcitabine drug resistance of a pancreatic cancer patient in an advanced stage, can improve the prognosis of the pancreatic cancer patient, can prolong the survival period of the pancreatic cancer patient in the advanced stage, and has important significance for the treatment of pancreatic cancer.

The invention discloses a tumor necrosis factor alpha detection kit using a chemiluminescence immunoassay technology, and relates to the technical field of detection kits. An anti-human tumor necrosis factor alpha antibody is used for coating a microporous ELISA plate, after a standard substance is added, the tumor necrosis factor alpha can be tightly combined with the coating antibody, then a detection antibody is added to form a stable antibody-antigen-enzyme-labeled antibody compound, free components are thoroughly removed through plate washing operation, then a chromogenic substrate TMB is added, and the detection sensitivity is high. The TMB is blue under the catalysis of a detection antibody, finally, the TMB is converted into yellow after a stop buffer is added, the depth of the color is positively correlated with the concentration of the tumor necrosis factor alpha in a sample, the absorbance is measured through an enzyme-linked immunosorbent assay instrument, the concentration of the sample can be accurately calculated, and the fixed seat can be prevented from shifting under the cooperation of a connecting shaft and a roller; and by arranging the bearing mechanism, the purposes of stretching out and storing the fixing mechanism can be achieved, and taking, placing and protection are facilitated.

Antibody-drug conjugates that bind to human oncology targets are disclosed. The antibody-drug conjugates comprise an antibody or an antigen-binding fragment thereof covalently linked to at least one BH3 mimetic through a dual linker. The disclosure further relates to methods and compositions for use in the treatment of cancers by administering the antibody-drug conjugates provided herein. Linker-drug conjugates comprising at least one BH3 mimetic and methods of making the same are also disclosed.

This application relates to the field of tumor grading and detection, specifically to the use of gene combinations in the manufacture of products for grading and detecting homologous recombination deficiency, tumor mutation burden, and microsatellite instability in human tumors. The gene combination consists of gene set A and gene fragment set B. The gene combination is obtained through specific pairwise clustering analysis from actual high-throughput sequencing data, and the data obtained from real-world data has higher reliability and certainty, enabling accurate grading and prediction of pan-cancer homologous recombination deficiency, tumor mutation burden, and microsatellite instability.

The purpose of the present disclosure is to develop a new combination therapy that exerts a superior antitumor effect as compared to administration of an anti-CD26 antibody alone. In order to assess both the function of an immune checkpoint inhibitor and the antitumor effect of an anti-CD26 antibody, it is necessary to be provided with both a binding site on a human CD26 molecule and an immune system of the same lineage of a cancer cell. Thus, in order to acquire data of an immune checkpoint inhibitor and an anti-CD26 antibody, it is essential to perform analysis in a human immune system and a human tumor cell line. The present inventors have made an attempt to produce a human immune system mouse to be used as a model animal for confirming the effect of the combination between ICI and an anti-CD26 antibody, and have successfully produced a model mouse superior for generating human T-cells. Next, the present inventors have studied the effect of combining an immune checkpoint inhibitor and an anti-CD26 antibody in a tumor bearing model by using said mouse. As a result, it was found that an agent using said combination has a synergistic effect that is stronger than when the respective agents are used individually.

The invention discloses an anti-NKG2D nano antibody, a fusion type nano antibody, a nucleic acid molecule, an expression vector, a recombinant cell and application thereof, and relates to the technical field of biological medicine. The anti-NKG2D nano antibody provided by the invention can specifically recognize and bind to NKG2D, can effectively competitively bind to a natural ligand (NKG2DL) of the NKG2D, and has relatively high affinity with the NKG2D. In-vitro experiments show that the provided antibody can effectively bind and activate NK cells so as to generate a remarkable killing effect on tumor cells. Therefore, the nano antibody provided by the invention can be applied to preparation of drugs for preventing or treating human tumors. In addition, the invention also provides a corresponding expression vector, a recombinant cell and an NKG2D detection product, an NKG2D enriched product and an NKG2D purified product related to the anti-NKG2D nano antibody, and the NKG2D detection product, the NKG2D enriched product and the NKG2D purified product have a wide application prospect.

A NOD.Cg-Prkdcscid NSG) mouse which is genetically modified such that the NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present invention. According to specific aspects the genetically modified NSG mouse is a NOD.Cg- Prkdcscid H2-K1tml Bpe H2-Ab1em Mvw H2-D1tml H2rg Wjl / SzJ NSG- RIP-DTR (IAnull) mouse, or a NOD.Cg-B2m'm" Une Prkdcscid H2dlAbl-Ea H2rg!"1 Wjl / SzJ (NSG- B2M ull (IA mouse. Human immune cells and / or human tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice. 20 24 20 47 25 09 J ul 2 02 4 A B S T R A C T 2 0 2 4 2 0 4 7 2 5 0 9 J u l 2 0 2 4

The invention discloses application of a thieno [2, 3-c] pyrazole compound in preparation of antitumor drugs, and belongs to the technical field of medical chemistry. The invention provides a small molecular skeleton thieno [2, 3-c] pyrazole compound I and a small molecular skeleton thieno [2, 3-c] pyrazole compound II, and the compound I is 2-oxobenzo [d] [1, 3] oxathiacyclopentane-6-yl 1-(3-fluorophenyl)-3-methyl-1H-thieno [2, 3-c] pyrazole-5-formate. And the compound II is 1-(4-chlorphenyl)-N-[4-((4-ethyl piperazine-1-yl) methyl) phenyl]-3-methyl-1H-thieno [2, 3-c] pyrazole-5-formyl. The two compounds have relatively strong anti-tumor activity. Wherein the compound II has a relatively strong inhibition effect on various human tumor cells such as osteosarcoma MG63, breast cancer HCC1806, liver cancer LM3, lung cancer A549, colorectal cancer HCT-8 and the like, and a new candidate compound is provided for broad-spectrum antitumor drugs.

This invention provides a recombinant transmembrane human tumor necrosis factor expressed in alfalfa. ‑α This method belongs to the field of biotechnology. This invention constructs a transmembrane human tumor necrosis factor... ‑α A plant binary expression vector for the gene is used, and then Agrobacterium-mediated transformation of the recipient alfalfa containing this plant binary expression vector is employed to prepare recombinant transmembrane human tumor necrosis factor. This invention utilizes alfalfa as a substrate plant for recombinant human tumor necrosis factor, providing a platform for recombinant transmembrane human tumor necrosis factor production. ‑α This provides an excellent cell system for expression, catering to the market demand for recombinant transmembrane trimeric tumor necrosis factor. ‑α This provides a new solution to the needs.

The application belongs to the technical field of biological medicine, and discloses a polypeptide specifically targeting a vascular marker molecule VEGFR2 and application thereof, wherein the amino acid sequence of the polypeptide is as follows: i) an amino acid sequence as shown in SEQ ID NO. 1; or ii) an amino acid sequence obtained by connecting a label to the N terminal or the C terminal of i); or iii) a functional polypeptide obtained by substituting, deleting and / or adding one or more amino acids in the amino acid sequence of i) or ii). The polypeptide provided by the application can target VEGFR2 positive cells, has high selectivity, and can be used as a target head of a targeted drug to increase the content of the drug in human tumor vascular marker molecule VEGFR2 positive cells. The polypeptide has high targeting property, simple preparation method and low cost, and therefore has good practical application value.

The invention discloses a biological sample whole RNA normal-temperature long-term preservative as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The preservative comprises the following components: a tissue fixing agent, a tissue penetrating agent, a reactive biological sample encapsulating agent, a silicification blocking agent, a pH regulator, an ion concentration regulator and water. The preservative can be applied to bacteria, such as escherichia coli and staphylococcus aureus; a cell, such as an HEK293 cell, an ID8 cell; tissues such as mouse liver tissues and human tumor tissues; organs such as kidneys and hearts of small animals; the whole RNA of a complete organism, such as earthworms, fruit flies and other biological samples with different sizes can be stored at normal temperature for a long time, so that the RNA extraction efficiency and quality can be ensured, the method is particularly suitable for normal-temperature transfer and long-term storage of field collected samples and clinical submitted samples, and the RNA extraction efficiency and quality in subsequent molecular experiments can be ensured; the method is of great significance to molecular biology research and clinical diagnosis.

NEO-201 is a humanized IgG1 monoclonal antibody (mAb) that is highly reactive against the majority of tumor tissues from a number of different cancer tumors, including colon, pancreatic, gastric, lung, breast and uterine cancers, but the majority of normal tissues are not recognized by such antibodies. Functional assays reveal that NEO-201 is capable of mediating both antibody dependent cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft tumors in vivo is greatly weakened by using NEO-201 alone and in combination with human peripheral blood mononuclear cells (PBMCs) that are effector cell sources for ADCC. In-vivo biological distribution research in mice carrying human tumor xenografts reveals that NEO-201 is preferentially accumulated in tumors rather than organ tissues. Single dose toxicity studies in non-human primates demonstrate the safety and tolerance of NEO-201 because the transient reduction of circulating neutrophils is the sole associated side effect observed.

The present disclosure provides a proteolysis-targeting compound TPB-L-E3B, a method for synthesizing the same, and use thereof. The compound can treat human tumor diseases through the eRF3a-targeting proteolysis mechanism, and exhibits great potential in treating such diseases in in-vitro studies, particularly, in treating diseases such as prostate cancer, ovarian cancer, liver cancer, cervical cancer, leukemia, breast cancer, and the like.

The invention discloses application of sulfonamide pyrrole compounds in preparation of anti-cancer drugs, and belongs to the technical field of medical chemistry. The invention provides sulfonamide pyrrole small molecule compounds with broad-spectrum anti-tumor potential, namely a compound I and a compound II. In-vitro pharmacological experiment results show that the compound I and the compound II show remarkable proliferation inhibition activity on various human tumor cell lines such as breast cancer HCC1806, osteosarcoma MG63, colorectal cancer HCT-8, liver cancer LM3 and lung cancer A549, and the inhibition effect is concentration-dependent. The results show that the sulfamido pyrrole compound has a good application prospect in research and development of anti-tumor drugs, and can be used as a candidate molecule for developing novel broad-spectrum anti-tumor drugs.

The invention provides an mRNA (messenger Ribonucleic Acid) medicine for inhibiting tumor stem cells and reducing the dryness of the tumor cells and a preparation method of the mRNA medicine. The mRNA medicine comprises any one or a combination of at least two of linear PTEN mRNA, self-replicating PTEN mRNA and annular PTEN mRNA; the linear PTEN mRNA comprises a 5 'UTR (Untranslated Region) sequence, a PTEN protein coding sequence and a 3' UTR sequence; the nucleotide sequence of the PTEN protein coding sequence comprises a sequence as shown in SEQ ID NO. 1. The mRNA nano-drug prepared by the invention not only has high transfection efficiency in tumor stem cells, but also can induce differentiation of the tumor stem cells and remarkably inhibit growth of the tumor stem cells; in drug-resistant tumor cells, the stemness of the drug-resistant tumor cells is inhibited, so that the sensitivity to chemotherapy, targeted antibodies, immunotherapy and the like is improved, and the killing effect of the drug is improved. The invention also shows an excellent anti-tumor effect in a human tumor cell line xenotransplantation model of the drug-resistant breast cancer in vivo, and provides a promising treatment strategy for the treatment of the drug-resistant breast cancer.