1702 results about "Solid tumor" patented technology

A pharmaceutical composition comprising a protein arginine methyltransferase 5 (PRMT5) inhibitor and a KRASG12C (Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine) inhibitor. The pharmaceutical composition can be used for treating various cancers, comprising solid tumors. The combined product can be used for treating any number of diseases associated with PRMT5 and / or KRASG12C.

The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. Included is a method of treating tissue with electrical energy, the method comprising: delivering electrical energy to tissue using one or more electroporation devices comprising one or more electrodes; and cooling the tissue, surrounding tissue, one or more of the electrodes, or one or more of the electroporation devices to minimize heating. In embodiments, the invention can be used to treat solid tumors, such as brain tumors, and in some embodiments, exemplary methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors.

The present invention relates to methods of immunomodulation and treating patients having solid tumors with antibodies that specifically bind CD38.

The present disclosure features a combination therapy useful for the treatment of solid tumors.

The invention discloses a nanometer antibody targeting FAP, a CAR-T cell and application of the nanometer antibody and the CAR-T cell. The invention provides nano-antibodies VHH1 and VHH2 capable of simultaneously recognizing human or mouse FAP. The nano-antibodies VHH1 and VHH2 are used as antigen binding regions to be constructed in a human or mouse CAR structure, and human or mouse FAP-CAR-T cells with a killing function can be prepared. Results of the mouse FAP-CAR-T cell or the human FAP-CAR-T cell provided by the invention show that the FAP-CAR-T cell has a good treatment effect on removal of FAP positive cells, and is a novel FAP-CAR-T cell which is expected to be applied to clinical solid tumor CAR-T therapy.

The invention provides a child abdominal common solid tumor activity image evaluation method and device and a medium, and the method comprises the steps: capturing the change information of a focus on a vein phase image after plain scanning and enhancement through a 3D convolutional neural network model, carrying out the intelligent silhouette, and generating an enhancement region and the enhancement degree of the focus after chemotherapy, thereby achieving the evaluation of the activity of a child abdominal common solid tumor. And finally, integrating all the information to perform intelligent diagnosis, judging the tumor activity, and forming an artificial intelligence auxiliary activity evaluation scheme after chemotherapy of the abdominal solid tumor. According to the method, the automatic enhancement degree quantitative evaluation of the hepatoblastoma, the nephroblastoma and the neuroblastoma of the children is realized through automatic tumor segmentation and registration subtraction image calculation by utilizing the plain scanning and enhanced CT image, so that the focus characteristics are extracted from multiple angles, the image information is fully mined, and the accuracy of the diagnosis is improved. Accuracy and sensitivity of activity discrimination after chemotherapy of the solid abdominal tumor of children can be obviously improved.

A two-stage multi-task learning based method is disclosed for automated lesion response assessment according to Response Evaluation Criteria in Solid Tumors (RECIST). Pre-processed venous phase CT scans are inputted into a convolutional neural network (CNN) and a transformer to obtain coarse lesion segmentation masks, which are then optimized by a multi-task learning framework that incorporates longitudinal CT correlation and clinical prior knowledge to generate difference maps, and adopts an ordinal regression strategy that encodes the ground truth of response outcome. Sum of the volume (SOV) -based response assessment and new lesion assessment results are combined to obtain the overall RECIST response, i. e., response, stable disease, and progressive disease.

The present disclosure provides compounds having activity as inhibitors of the G12C mutant KRAS protein, pharmaceutical compositions comprising the compounds, and methods of treating certain disorders, such as cancer, including but not limited to lung cancer, pancreatic cancer, colorectal cancer, and solid tumors. In particular, the disclosure provides compounds of Formula (I):, and pharmaceutically acceptable salts thereof, wherein the substituents are as described.

The invention discloses a medical developing marker and a manufacturing method thereof, and relates to the field of medical instruments, the medical developing marker comprises a closed tube, the outer wall of the closed tube is provided with a bionic barb structure, the bionic barb structure is distributed in a flexible zigzag convex manner, and the bionic barb structure and the closed tube are integrally formed through an injection molding process; a closed cavity is arranged in the closed tube, four developing strips are symmetrically arranged in the tube wall of the closed cavity, the tube wall of the region where the developing strips are located is etched to form a weak band, and a developing material layer and a sustained-release medicine layer are sequentially deposited at the weak band. The developing material layer and the sustained-release drug and / or marked nano-particle layer are alternately deposited to form a functional composite layer, and the functional composite layer can directionally rupture to release the therapeutic drug under the action of implantation pressure. The marker integrates the functions of precise development, tissue anchoring and drug sustained release, is adaptive to multi-mode imaging such as ultrasonic imaging, X-ray imaging, CT imaging, MRI imaging and PET-CT imaging, and has remarkable clinical value in precise positioning treatment of solid tumors such as breast cancer and liver cancer.

The invention belongs to the technical field of medical pathological images, and particularly relates to a multi-instance multi-task learning pan cancer biomarker prediction method and system, and the method comprises the steps: obtaining a full-view digital pathological image and pan cancer biomarker expression data of a solid tumor patient; performing preprocessing and feature extraction based on the full-view digital pathological image to obtain a pathological feature data set; based on the pathological feature data set, inputting the pathological feature data set into a twin multi-example full convolutional network model for training to obtain pathological low-dimensional features, and calculating an attention score corresponding to each pathological feature in combination with a linear attention mechanism; and in combination with each pathologic low-dimensional feature and the corresponding attention score, calculating to obtain a pathologic depth feature, and inputting the pathologic depth feature into a multi-task classification prediction model for classification prediction to obtain a prediction result of each biomarker in the pan cancer.

The invention discloses a lysosome targeted chimera based on Sortilin and application thereof. The lysosome targeted chimera comprises a ligand molecule of a lysosome targeted receptor and a ligand molecule of a targeted protein to be degraded, wherein the ligand molecule and the ligand molecule are connected through a linker; the lysosome targeting receptor is Sortilin, and the ligand molecule of the lysosome targeting receptor is a polypeptide targeting the Sortilin; the protein to be degraded is membrane protein or extracellular protein. Furthermore, the polypeptide of the targeted Sortilin is connected with an enzyme response sequence and an integrin receptor targeting sequence. According to the invention, the Sortilin-combined ligand neurotensin is functionally coupled with the neutralizing antibody or polypeptide of overexpression protein in targeted tumor or inflammatory diseases, and the Sortilin-combined ligand neurotensin has obvious treatment gain in malignant solid tumor and psoriasis models. The discovery promotes the transformation potential of the lysosome participating in the biological agent, and provides a dual strategy for realizing accurate degradation through receptor recruitment and microenvironment induction.

The invention discloses a bispecific cytokine fusion protein, which comprises an amino acid sequence of a type I cytokine and an amino acid sequence of a type II cytokine, and the amino acid sequence of the type I cytokine and the amino acid sequence of the type II cytokine are directly connected through a connecting peptide or are connected in series or in parallel through a fusion partner and the connecting peptide. Amino acid sequences of type I and type II cytokines are connected in series or in parallel to form the bispecific cytokine fusion protein, and the fusion protein can synergistically activate precursor depleted CD8 + T cells and terminal depleted CD8 + T cells, improve immunosuppression of a solid tumor complex microenvironment and release the potential of tumor immunotherapy. The invention further discloses nucleic acid, a carrier, a cell, a medicine or a medicine composition related to the bispecific cytokine fusion protein. The invention also discloses application of the bispecific cytokine fusion protein in preparation of drugs for treating cancers.

Provided herein are novel cyclic peptides, their synthetic process, compositions, properties including stability and pharmacokinetic profiles, and applications for treating solid tumor cancers.

The invention discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver cancer.

Provided is a recombinant human serum albumin-collagen binding domain (CBD) fusion protein for tumor-specific targeting matrix and its use in specific targeted treatment of a solid tumor. HSA and the CBD generate gene fusion in the form of different molecular structures, and can be expressed in a constructed recombinant engineered host. A pharmaceutical recombinant fusion protein is obtained through large-scale fermentation. The recombinant fusion protein shows tumor-specific targeting of solid tumors and can be used as a starting material of a broad-spectrum matrix carrier. The recombinant fusion protein is coupled with any tumor treatment drug, small-molecule compound, or cytotoxic protein to form an innovative pharmaceutical composition. The pharmaceutical composition of the recombinant fusion protein is also long-acting, can prolong a half-life of the conjugate drug in vivo, and has a significantly better clinical curative efficacy on anti-tumor than that of a monomer drug.

The invention belongs to the technical field of biomedical treatment, and discloses a preparation method of immunomodulatory recombinant macrophage vesicles, and the preparation method specifically comprises the following steps: step 1, clinical sequencing of gingival tumor tissues and pathogenic microbiota data analysis; hybridizing and fusing a macrophage membrane infected by the porphyromonas gingivalis and an exosome membrane; and 3, constructing a piezoelectric driven ROS (reactive oxygen species) to generate the immunoregulation vesicles. The invention provides an innovative nano vesicle technology, and the technology shows double advantages in tumor treatment: firstly, accurate targeting and efficient killing of key porphyromonas gingivalis in a tumor environment are realized by constructing recombinant macrophage vesicles, and meanwhile, the stability of normal flora is kept, and tumor deterioration is prevented; and secondly, the anti-tumor immune response is obviously activated by utilizing the immunoregulation capability of the bacteria-induced macrophages and exosome vesicles thereof, including converting immunosuppressed M2 type macrophages into anti-tumor M1 type macrophages, so that the growth of solid tumors is effectively inhibited.

The invention relates to the technical field of tumor neoantigen detection, and particularly discloses a neoantigen prediction method and system for a malignant solid tumor, and the method comprises the following steps: obtaining a tumor sample and a peripheral blood sample, and carrying out DNA and RNA sequencing; analyzing and processing to obtain DNA (Deoxyribonucleic Acid) sequencing data and RNA (Ribonucleic Acid) sequencing data; analyzing to obtain an HLA typing result and a sequence of the mutant protein; calculating to obtain related characteristic values of the new antigens; calculating a new antigen score; and intercepting the first N pieces with the highest scores to obtain a neoantigen prediction result of the malignant solid tumor. Starting from the action mechanism of the new antigens, according to key steps of the prediction process, a plurality of characteristic values are selected, a hard filtering index is not adopted, a product mode is adopted, and the score of the new antigens is calculated according to the score of the relevant characteristic values of the new antigens.

The invention relates to the field of tumor cell therapy, in particular to application of T lymphocyte chimeric with a B7-H3 receptor to treatment of head and neck tumors, and provides an anti-B7-H3 scFv, the scFv comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an HCDR region and an HFR region, and the light chain variable region comprises an LCDR region and an LFR region; compared with a wild type scFv sequence, the scFv sequence has the advantage that a plurality of amino acids with positive charges in the HFR region and / or the LFR region are mutated into amino acids without charges. According to the invention, positive charge plaques on the CAR surface of an scFv sequence of a B7-H3 human-derived monoclonal antibody MGA271 are changed in a charged amino acid mutation manner, so that a B7-H3. CAR-T cell is optimized, and it is proved that the B7-H3. CAR-T cell optimized by PCP can effectively kill B7-H3 positive tumor cells in vivo and in vitro; and a new method and thought are provided for clinical targeted treatment of B7-H3 positive solid tumors.

The invention belongs to the field of biomedicine, and particularly relates to polypeptide for targeted blocking of combination of TRIM25 and BRD7 protein and application of the polypeptide. According to the present invention, based on the minimum binding region PRYSPRY structural domain (439 aa-630 aa) of the TRIM25 and the BRD7 protein, the blocking peptide TB16 capable of specifically blocking the mutual binding of the TRIM25 and the BRD7 protein is screened, such that the ubiquitination degradation of the BRD7 is inhibited, and the stability of the BRD7 tumor inhibition protein is improved. The polypeptide drug TB16 can effectively inhibit breast cancer, nasopharynx cancer, ovarian cancer, lung cancer and liver cancer cell proliferation and breast cancer in-vivo tumor growth, has good anti-solid tumor activity, and is expected to become a new anti-tumor targeting drug.

The invention discloses a CAR-T cell and an application thereof. According to the application, nano antibodies VHH1 and VHH2 capable of simultaneously recognizing human or mouse FAP are used as antigen binding regions to be constructed in a human or mouse CAR structure, and human or mouse FAP-CAR-T cells with a killing function are obtained. The mouse FAP-CAR-T cell or the human FAP-CAR-T cell provided by the invention has a good treatment effect on removal of FAP positive cells, and is a novel FAP-CAR-T cell which is expected to be applied to clinical solid tumor CAR-T therapy.

An antibody capable of binding to LILRB4 and a bispecific antibody capable of binding to LILRB4 and CD3 are provided. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. Also provided are methods of treating solid tumors, multiple myeloma or leukemia, such as acute myelogenous leukemia (AML), using the anti-LILRB4xCD3 double antibodies of the present invention.

Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) is determined for each somatic mutation based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the test subject is determined based on the set of VAFs for the one or more somatic mutations.

The present invention relates to the field of optical imaging. More specifically, the present invention relates to a class of monoalkylated cyanine dyes having red to near-infrared (650-900 nm) emission, characterized by pH responsiveness, and to conjugates thereof with biological ligands. The present invention also relates to the use of these compounds as optical diagnostic agents in the imaging or therapy of solid tumors, to methods for their preparation and to compositions containing them. The monoalkylated cyanine dyes have the general formula (I), in which R1 and R3 are independently selected from the group consisting of hydrogen, -SO3H, -COOH and -CONH-Y; and R2 and R4 are hydrogen, or R1 together with R2 and R3 together with R4 both form two aryl rings optionally substituted by 1 to 4 -SO3H groups together with the atoms to which they are bonded; R5 is an alkyl group optionally substituted by a group selected from -SO3H, -COOH and -CONH2. #imgabs0#

The invention provides a CLDN6 single domain antibody and a humanization method thereof. The CLDN6 single-domain antibody provided by the invention has targeted specificity to CLDN6, only recognizes the CLDN6 and does not recognize CLDN3, CLDN4 and CLDN9 of the same family, or the recognition modes are obviously different. The CLDN6 single-domain antibody 1H07 with targeting specificity provided by the invention can be used for constructing a chimeric antigen receptor (CAR) and a bivalent antibody (bispecific antibody). The CAR constructed based on the antibody sequence can be transduced into a T cell to create a CAR-T cell specifically targeting CLDN6, and the CAR-T cell can be used for treating solid tumors such as ovarian cancer.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

The invention provides a preparation method and application of a CD70 specific nano antibody molecular imaging probe. The probe comprises a tumor targeting group, radionuclide and a bifunctional chelating agent, the tumor targeting group is a CD70 specific nano antibody; the CD70 specific nano antibody is R8B4, and the amino acid sequence of the R8B4 is as shown in SEQ ID No. 1. The probe provided by the invention can realize noninvasive diagnosis of solid tumors such as renal clear cell carcinoma and malignant tumors of a blood system; reabsorption of the compound in the kidney is effectively inhibited through charge adjustment, kidney uptake is remarkably reduced, non-specific signals are reduced, the signal-to-noise ratio during targeted imaging or treatment is increased, and the imaging quality and treatment safety are improved. The probe not only has a wide application prospect in tumor diagnosis, but also provides a new technical support for targeted therapy and individualized precision medical treatment, and has important scientific research and clinical application values.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and / or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and / or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin− and / or pagP−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd−, purI−, and msbB−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and / or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and / or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. Also provided are derivative cells having stable and functional genome editing that delivers improved or enhanced therapeutic effects. Further provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The invention discloses a construction method and application of a gastric cancer treatment effect evaluation model of CAR-T cells, and the constructed gastric cancer treatment effect evaluation model of the CAR-T cells comprises a CAR-T cell and gastric cancer organ co-culture killer dynamic detection system and a CAR-T cell, intestine organ and lung organ co-culture safety evaluation system. Based on a CAR-T cell and gastric cancer organoid co-culture lethality dynamic detection system, the process that CAR-T cells act on gastric cancer organoid can be dynamically observed through a living cell imaging method, then the action mechanism of the CAR-T cells for treating solid tumors is studied, and meanwhile, based on a CAR-T cell, intestine organoid and lung organoid co-culture safety evaluation system, the CAR-T cells and the gastric cancer organoid co-culture lethality dynamic detection system can be used for evaluating the CAR-T cells and the gastric cancer organoid co-culture lethality. Compared with the prior art, the preclinical model has the advantages that the effect of the CAR-T cells on gastric cancer para-tissues and other tissue-derived organs can be detected, and safety evaluation is carried out, so that the preclinical model for more comprehensively detecting the gastric cancer treatment effect of the CAR-T cells is obtained, and the research on CAR-T cell targets is facilitated.

The invention provides a preparation method and application of a modified chitosan derivative and nanoparticles thereof. The modified chitosan derivative is prepared by modifying chitosan with nitrogen-containing heterocyclic ring small molecules; the modified chitosan derivative nano-particles are prepared by electrostatic compounding of a modified chitosan derivative on an electronegative substance. The modified chitosan derivative and the nano-particles thereof have relatively strong immune activation capability on immune cells, and also can enhance the immunogenicity of tumor cells and effectively regulate the immune microenvironment of solid tumors. When the modified chitosan derivative and the nano-particles thereof are used in combination with radiotherapy, the modified chitosan derivative and the nano-particles thereof have relatively high tumor treatment efficiency.