38 results about "Tumor stroma" patented technology

The invention provides an aggregation-induced emission molecule, a nano motor and a preparation method and application of the aggregation-induced emission molecule, the aggregation-induced emission molecule is used for near-infrared emission, has photo-thermal properties, and has the characteristics of near-infrared II region luminescence, heat production and good light stability; the nano motor is prepared by taking an asymmetric double-mesoporous nano material with different pore diameters as a support material and selectively loading aggregation-induced emission molecules on one side of the support material with a larger pore diameter; under the irradiation of near-infrared light, the aggregation-induced emission molecules with the photothermal effect can form a non-uniform thermal gradient to push the self-thermophoresis movement of the nano motor; tumor sites can be diagnosed and reported under the mediation of near-infrared II region imaging; through the photo-thermal effect, the motor can destroy tumor interstitial cells and degrade tumor matrix components; and in combination with autothermophoresis, blood vessels can be penetrated, so that penetration to the deep layer of the tumor can be realized.

Described herein are methods, systems, and programming for determining a tumor immunophenotype of an image of a tumor. Some embodiments include dividing an image into tiles depicting tumor epithelium and / or tumor stroma. For each tile, an epithelium-immune cell density and a stroma-immune cell density may be calculated based on a number of immune cells identified in the tumor epithelium and the tumor stroma, respectively. Based on the epithelium-immune cell density and the stroma-immune cell density, an inflammation type of the type may be determined, and a tumor immunophenotype may be determined based on each tile's inflammation type.

The invention belongs to the field of biological medicine and ultrasonic medicine, and provides a barium titanate (BTO) piezoelectric material-based ultrasonic responsive targeting nano system (BTO at BAL), which is used for matrix microenvironment remodeling and immunopotentiation of compact tumors such as pancreatic cancer and the like. According to the nanoparticles, oleic acid modified BTO is taken as a core, ROS responsive prodrug molecules containing a small molecule PD-L1 inhibitor BMS1166 and a nitric oxide donor (Arg) 9 are loaded on the surface, and specific targeting on pancreatic cancer cells is realized by combining a targeting peptide LFC131. Under ultrasonic excitation, BTO generates reactive oxygen species (ROS), on one hand, (Arg) 9 is oxidized to release NO, tumor matrix is degraded, tumor hardness is reduced, drug delivery efficiency is improved, and meanwhile, ROS and NO synergistically enhance tumor immunogenicity; on the other hand, the ROS breaks a thioketal bond to release BMS1166, PD-L1 expression is down-regulated, and immunosuppression is reversed. According to the present invention, the significant tumor inhibition and immune activation effects are represented in the animal model, and the clinical transformation potential is provided.

In some embodiments, the present disclosure relates to a method. The method includes accessing digitized pathology imaging data from a cancer patient. The digitized pathology imaging data includes segmented imaging data that identifies one or more regions of interest (ROI) including tumor-stroma regions and / or collagen fibers. A plurality of collagen fiber features are extracted from the one or more ROI. The plurality of collagen fiber features are provided to a machine learning model that is trained to generate a medical prognosis relating to the cancer patient.

To provide compositions and methods for penetration, distribution and response of targeting particles in malignant brain tumors.SOLUTION: Described herein are nanoparticle conjugates that demonstrate enhanced penetration into tumor tissue (e.g., brain tumor tissue) and diffusion within the tumor interstitium, e.g., for treatment of cancer. Further described are methods of targeting tumor-associated macrophages, microglia, and / or other cells in a tumor microenvironment using such nanoparticle conjugates. Moreover, diagnostic, therapeutic, and theranostic (diagnostic and therapeutic) platforms featuring such nanoparticle conjugates are described for treating targets in both the tumor and surrounding microenvironment, thereby enhancing the efficacy of cancer treatment. Use of the nanoparticle conjugates described herein with other conventional therapies, including chemotherapy, radiotherapy, immunotherapy, and the like, is also envisaged.SELECTED DRAWING: None

Disclosed are a chimeric antigen receptor T (CAR-T) cell and a construction method thereof, and an antitumor drug. In the present application, aquaporin 3 (AQP3) is adopted as a novel anti-cancer target, and AQP3 is highly expressed in both tumor cells and tumor stromal cells and can mediate the transport of both water and glycerol, which is conducive to breakage of a physical barrier of a tumor and promotes CAR-T cells to well infiltrate into a tumor to kill the tumor. The chimeric antigen receptor (CAR) fusion protein of the present application can be used in the treatment of AQP3-positive malignant tumors, and especially, when used in the treatment of non-small cell lung cancer (NSCLC), the CAR fusion protein exhibits a significant therapeutic effect. In addition, when used in the treatment of lung cancer, the CAR fusion protein causes little damage to a normal tissue and exhibits high safety.

This invention discloses an enzyme- and pH-responsive nucleic acid loading and delivery material and its preparation method. The material can be used for efficient loading and delivery of nucleic acid molecules. The preparation method uses amphiphilic zwitterionic monomers to improve the reverse emulsion polymerization system, enhancing polymerization at the two-phase interface and avoiding the extrusion effect of polymerization in the aqueous core on nucleic acid molecules, thereby improving the loading efficiency of nucleic acid molecules. Further preparation of cross-linking agents MP-CL and CB-CL, which can cleave in response to matrix metalloproteinase II or cathepsin B, endows the nanogel with the ability to respond to charge reversal in the tumor matrix and to release nucleic acid molecules from tumor cells. The acid-sensitive blocks on the amphiphilic monomers give the nanogel lysosomal escape capability. The delivery material can efficiently deliver nucleic acid molecules into cells and exhibits excellent stability and biosafety.

The invention discloses an engineered exosome preparation with tumor targeting and specific gripper response release functions as well as a preparation method and application of the engineered exosome preparation. The preparation comprises a myocardial cell exosome, an NK cell biotinylation activation antibody, a tumor disease biotinylation antibody, streptavidin, a tumor fiber matrix FAP targeting peptide and a tumor matrix enzyme response peptide, and anchoring is carried out through an acetamide compound-polyethylene glycol anchor point platform. The engineering bispecific exosome preparation with good tumor targeting and barrier breakthrough ability and immune cell activation effect is prepared, and the preparation breaks a solid tumor compact fiber barrier and increases NK cell infiltration by utilizing the fibrosis treatment ability of the myocardial cell exosome and the capture and targeting effects of an anchor point platform; the natural killer cells are in close contact with tumor cells, the lasting tumor cell killing effect is achieved, and the tumor matrix environment is fundamentally changed.

The invention belongs to the technical field of biological medicines, and particularly relates to a pharmaceutical composition containing carboxamide triazole or pharmaceutically acceptable salts thereof and application of the pharmaceutical composition in preparation of medicines for preventing or treating fibrosis-related diseases. Specifically, the invention discovers that the carboxylamine triazole orotate (CTO) can directly inhibit fibroblast collagen generation and cross-linking maturation, so that the fibrosis degree is reduced; when the polypeptide is combined with a PD-1 antibody, collagen deposition in tumor tissues can be reduced by inducing normalization of a tumor matrix in a synergistic manner, the tumor permeation concentration of chemotherapeutic drugs is remarkably enhanced, and the anti-tumor curative effect is improved. The invention can be applied to the treatment of various matrix dense solid tumors including pancreatic cancer, breast cancer, colorectal cancer and lung adenocarcinoma, and is expanded for intervention of fibrosis-related diseases, thereby providing a new treatment strategy for improving the efficacy of chemotherapeutic drugs and improving immunotherapy response through targeted matrix remodeling.

The present invention relates to multi-specific T cell engagers and the use thereof. Specifically, the present invention provides the multi-specific T cell engager, comprising a first targeting domain targeting leucine-rich repeat containing protein 15 (LRRC15) molecules highly expressed on the surface of a tumor cell, and further comprising a second targeting domain and / or a third targeting domain bound to the CD molecules of T cell surface. The LRRC15 related multi-specific T cell engagers of the present invention can effectively activate T cells and reduce the tumor stroma impact, and can be used as an effective therapeutic agent for treatment of tumors, especially tumors with a high expression level of LRRC15.

The invention discloses a bionic photo-thermal nano motor for targeted regulation and control of a solid tumor matrix-immunosuppression microenvironment and a preparation method and application thereof, and belongs to the technical field of biomedical materials.The preparation method comprises the steps that polydopamine nanoparticles and a K2PtCl4 aqueous solution are subjected to condensation reflux, and asymmetric PDA-Pt is prepared; and preparing a cancer-related fibroblast and breast cancer cell fusion membrane and coating the surface of PDA-Pt with the cancer-related fibroblast and breast cancer cell fusion membrane. The nano-motor realizes dual targeting of matrix cells and tumor cells through a surface modified fusion cell membrane, targeted ablation CAFs regulates and controls a tumor matrix microenvironment, a good tumor permeation effect is realized by cooperating with H2O2 responsive self-driving of the nano-motor, a mild photo-thermal-catalytic synergistic effect is formed by a photo-thermal effect of PDA and peroxidase-like activity of Pt nano-enzyme, and a good tumor permeation effect is achieved. And finally, the tumor immunosuppression microenvironment is remarkably improved, and the tumor immunotherapy effect is improved.

The dual therapy involving tumor stroma-binding IL-7 and IL-12 variants led to synergistic antitumor efficacy through suppression of immune exhaustion and promotion of immune memory without compromised tolerability. The disclosure describes a polypeptide comprising an IL-7 polypeptide, or a functional fragment thereof, linked to a extracellular matrix (ECM)-affinity domain. Also described is a nucleic acid encoding a polypeptide of the disclosure and cells comprising the polypeptide(s) or nucleic acid(s) of the disclosure.

The invention discloses hydrogel for culturing tumor organoids as well as a preparation method and application of the hydrogel. The preparation method comprises the following steps: mixing norbornene functionalized hyaluronic acid, enzyme digestion polypeptide matched with tumor matrix degradation, cell adhesion peptide and a photoinitiator, and carrying out a cross-linking reaction to obtain the hydrogel for culturing tumor organoids. The hydrogel prepared by the method disclosed by the invention is clear in component, and a three-dimensional network structure is obtained by gelatinizing hyaluronic acid, tumor characteristic enzyme digestion polypeptide and cell adhesion mimic peptide through a sulfydryl-olefin chemical reaction. The hydrogel prepared by the invention has the characteristics of fast gelation, enzyme sensitivity, adjustable mechanical properties and good biocompatibility under the action of the modified peptide, can be used as a substitute of matrigel for three-dimensional culture of tumor organs, and is applied to sensitivity detection of chemotherapeutic drugs.

The invention discloses a bispecific antibody modified tumor cell-derived drug-loaded vesicle and a preparation. The tumor cell-derived drug-loaded vesicles comprise vesicles released by apoptotic tumor cells and antitumor drugs wrapped in the vesicles and used as effective components; the vesicles are modified with a bispecific antibody through DSPE-PEG-NH2, and the bispecific antibody can achieve a synergistic effect with an anti-tumor drug wrapped by the vesicles at a targeting part of the vesicles; the bispecific antibody is a PD-L1 / TGF (Transforming Growth Factor)-beta bispecific antibody. The tumor cell-derived drug-loaded vesicle provided by the invention can target tumor tissues, responds to release a bispecific antibody in a tumor subacid environment, and reduces tumor matrix components by regulating and controlling tumor-related fibroblasts, so that the enrichment and deep penetration of the drug-loaded vesicle at a tumor part are increased.

Disclosed in the present invention are a FAP-targeting compound and a preparation method therefor. By means of a meticulously designed molecular structure containing a plurality of variable substituents, the compound can precisely target fibroblasts in tumor stroma, thereby providing a new approach for cancer treatment. The Z group of the compound can be flexibly replaced by a radioactive agent, fluorescent agent or contrast agent, thus broadens the application range for tumor diagnosis and treatment. In the preparation method, starting from a starting material, a high-purity and high-yield FAP-targeting compound is ultimately obtained via a plurality of efficient reaction steps. Such compound has good metabolic stability and pharmacokinetic properties, which reduce the side effects of medications and increase the therapeutic effect. The diverse substituents and linker arms of the compound further optimize the physicochemical properties and improve the overall therapeutic effect. When combined with a pharmaceutical carrier, the compound achieves efficient delivery to tumor tissues and reduces non-target side effects, which provides a precise and effective personalized treatment regimen for cancer patients, and significantly improves the therapeutic effect and the quality of life of patients.

The dual therapy involving tumor stroma-binding IL-7 and IL-12 variants led to synergistic antitumor efficacy through suppression of immune exhaustion and promotion of immune memory without compromised tolerability. The disclosure describes a polypeptide comprising an IL-7 polypeptide, or a functional fragment thereof, linked to a extracellular matrix (ECM)-affinity domain. Also described is a nucleic acid encoding a polypeptide of the disclosure and cells comprising the polypeptide(s) or nucleic acid(s) of the disclosure.

The present invention relates to a multimodal non-invasive in vivo system and related method for the characterization of the tissue microenvironment. The system comprises: a multispectral imaging (MSI) camera for superficial spectral screening; a multispectral optoacoustic tomography (MSOT) module for dynamic vascular and perfusion analysis; a Mueller Matrix Polarimetry (MMP) module for extracellular matrix anisotropy assessment; a Raman spectroscopy module for molecular fingerprinting of fibroblast-associated proteins; an optical coherence tomography (OCT) module for morphological and stratigraphic evaluation; an optional Elastic Scattering Spectroscopy (ESS) module for subcellular scattering biomarkers; and a diachronic analysis module for longitudinal monitoring. Data are integrated by an artificial intelligence processing unit to generate quantitative biomarkers of vascularization, extracellular matrix features, immune activity (Langerhans cells) and fibroblast phenotype, distinguishing physiological myofibroblasts from CAF. The invention enables non-nvasive, biopsy-free evaluation of scars, melanocytic lesions, tumor stroma, wound healing and surgical site monitoring.

Disclosed are methods and systems for selecting one or more candidate regions from a tissue for inclusion in a tissue microarray (TMA). Methods involve determining tissue compositions of regions across the tissue and selecting the candidate regions that have desired tissue compositions for inclusion in a TMA. For example, desired tissue compositions can include one or more tissue classes, examples of which include tumor, stroma, immune, necrosis, other tissue, or combinations thereof. Thus, the disclosed method represents an automated process of selecting candidate regions without involving manual input.

The present application relates to the technical field of digital image processing, in particular to a tumor interstitial proportion quantitative evaluation system based on pathological images. The present application automatically obtains tumor epithelial region, tumor interstitial region, tumor region and tumor infiltration front region based on image segmentation, without pre-selecting histological evaluation position for visual evaluation by artificial selection, avoiding the subjective experience dependence of traditional methods, and improving the efficiency of tumor interstitial proportion evaluation. In addition, the present application comprehensively quantitatively evaluates the first tumor interstitial proportion under the overall scale of the to-be-tested pathological image, the second tumor interstitial proportion under the scale of the tumor infiltration front region and the third tumor interstitial proportion under the scale of the tumor region, and finally obtains the tumor interstitial proportion score value which can reflect the tumor interstitial proportion characteristics of different anatomical positions, further improving the accuracy of the evaluation result. The preset rule is to select the window tumor interstitial proportion with the highest tumor interstitial proportion value.

The present disclosure relates to methods of coupling antic-cancer agents and anti-cancer treatments to improve the efficacy of the overall treatment. The anti-cancer agent reduces stroma in the tumor microenvironment, in part by killing stroma producing cells such as TAFs and TAMs. Reduction of tumor stroma not only improves immune cell function, including immune cells administered in a second treatment, but also allows allowing other anti-cancer treatments to better access to tumor cells.

The present invention relates to methods of obtaining an indication of the prognosis of a breast cancer subject, for classifying breast tumours, and related methods. The methods are based on the production of a signature score which is derived from normalised expression levels of a plurality of specific breast tumour stromal protein or tumour stromal RNA biomarkers.

The present disclosure relates to cancer tumor stroma models with dense stroma and heterogeneous patterns of ECM anisotropy. The invention herein will enable more accurate modeling of tumor pathophysiology, drug delivery, and novel treatment methods impacted by ECM density.

A tumor stroma imaging agent with a chemical structural formula (I):is provided, where R is hydrogen or fluorine. Compared with the prior art, the tumor stroma imaging agent exhibits significant affinity for fibroblast activation protein (FAP), high uptake for a malignant tumor with high FAP expression in a tumor stroma, and high sensitivity and specificity for the diagnosis of a malignant tumor, and is not prone to false positives. Therefore, the tumor stroma imaging agent can be effectively and safely used for the diagnosis and treatment of various malignant tumors with a prolonged half-life and an extended window period, which is conducive to clinical application.

The invention discloses application of an FMR1 inhibitor in preparation of a medicine for treating immunological rejection type gastric cancer. Experimental studies prove that FTO is continuously and highly expressed in immunological rejection phenotypes and is related to interstitial activation and T cell rejection. Continuous immunohistochemistry and multiple immunofluorescence show that the FMR1 protein is highly expressed in an immunological rejection type tumor microenvironment, and most CD8 + T cells are located in tumor interstitial substances. In mechanism, the FMR1 regulates and stabilizes FTO protein and limits the degradation of proteasome of the FTO protein through post-translation, so that FTO-dependent m6A reprogramming is maintained, and an immunological rejection microenvironment is enhanced. Therefore, the invention discloses a non-classical mechanism that the FMR1 modifies and stabilizes the FTO protein after translation, and the FMR1-FTO axis can be used as a potential intervention target for breaking an immune barrier and sensitizing gastric cancer immunotherapy.

The invention belongs to the technical field of medicines, and particularly relates to nanoparticles for treating pancreatic cancer by utilizing enamine N-oxide to trigger transendocytosis and cross-matrix barrier as well as a preparation method and application of the nanoparticles. The nano particle is prepared by self-assembly of an amphiphilic block polymer and hydrophobic drugs GemC18 and Galunissertib, and the amphiphilic block polymer and the hydrophobic drugs GemC18 and Galunissertib are used as auxiliary materials. The chemotherapeutic drug is a hydrophobic prodrug GemC18 of a pancreatic cancer clinical first-line chemotherapeutic drug gemcitabine, the drug for regulating and controlling tumor matrix hyperplasia and immunosuppression is Galunissertib, and the polymer is an amphiphilic block polymer which is obtained through ring-opening polymerization reaction of N-carboxy anhydride (NCA), is modified by enamine N-oxide and has hypoxia response charge turnover capacity. And the GemC18 and the Galunissertib are assembled together with the pi-pi cationic polymer through a hydrophobic effect, so that the nanoparticles are formed. The nanoparticles can trigger an adsorption-mediated transendocytosis cross-matrix barrier, simultaneously respond to hypoxia, consume GSH (glutathione), up-regulate ROS (reactive oxygen species), correct charges, improve intra-tumor permeation of drugs, remodel a matrix and reverse immunosuppression.

The application provides a pancreatic cancer deep penetration ferroptosis nano preparation and a preparation method and application thereof, the nano preparation comprises a drug-loaded core and a MOF shell, the drug-loaded core is formed by polymerization of a ferroptosis inducer Erastin and a polymer material, and the MOF is formed by coordination of iron ions and tannic acid. The preparation method is as follows: iron ions, the polymer material and Erastin are mixed to form an organic phase solution, the solution is slowly dropped into a tannic acid aqueous phase solution, and the nano preparation is obtained through ultrasonic and stirring. The nano preparation constructed in the application can regulate the re-polarization of tumor-associated macrophages, thereby reducing the activation and collagen deposition of tumor-associated fibroblasts to regulate the dense tumor stroma, achieving deep penetration of the nano preparation, after reaching the deep part of the tumor, the iron ions and Erastin synergistically act to destroy the redox balance of tumor cells, improve the ferroptosis effect of tumor cells, and realize ferroptosis treatment of pancreatic cancer cells.

The present invention relates to a multispecific antibody containing an LRRC15 antigen-binding domain and the use thereof. Particularly, provided in the present invention is a multispecific antibody, which contains a first targeting domain that targets to a leucine-rich repeat containing 15 (LRRC15) molecule highly expressed on the surface of a tumor cell, also contains a second targeting domain that binds to a CD40 molecule on the surface of an antigen presenting cell (APC) or a CD3 molecule on the surface of a T cell, and optionally, contains a third targeting domain that targets to PD-1, CLDN18.2 or FAP, and / or a fourth targeting domain that targets to TGF-β. The LRRC15-related multispecific antibody of the present invention can effectively activate T cells and reduce tumor stroma impact, thereby providing effective treatment for tumors and fibrotic diseases.

The invention discloses application of fibroblast-MMP11 in pancreatic cancer angiogenesis and tumor cell heterogeneity and metastasis, relates to the technical field of biological medicine, and discloses application of fibroblast-MMP11 in pancreatic cancer angiogenesis and tumor cell heterogeneity and metastasis. Preferably, the drug targets the FbMMP11 or the VEGF and NOTCH signal channels activated by the FbMMP11. According to the application of the fibroblast-MMP11 as the pancreatic cancer diagnosis marker, prognosis and metastasis risks of patients are evaluated by detecting the expression level of the FbMMP11. The invention relates to a pharmaceutical composition for inhibiting angiogenesis and metastasis of pancreatic cancer. The pharmaceutical composition comprises an inhibitor targeting FbMMP11 and a VEGF / NOTCH signaling pathway blocker. In the invention, the molecular basis of the FbMMP11 subgroup for promoting tumor matrix fibrosis through high expression of collagen synthesis genes such as COL1A1 and INHBA is defined; secondly, a new mechanism that FbMMP11 promotes tumor angiogenesis by activating VEGF and NOTCH signal pathways in EnCOL15A1 endothelial cells is disclosed.

The tumor stroma, which occupies a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, particular emphasis is on a subset of stromal cells, called cancer-associated fibroblasts, which are present in more than 90% of epithelial cancers, including pancreatic, colon, and breast cancers. Cancer-associated fibroblasts are characterized by high expression of FAP, which is not detectable in normal adult tissues but is associated with poor prognosis in cancer patients. The present invention provides small molecule radiopharmaceuticals and imaging agents based on FAP-specific inhibitors.

A method for preparing biomimetic nanocomposite materials based on thylakoid membranes is disclosed, belonging to the field of bionanomaterials technology. This invention addresses the problems of existing nano-manganese oxide, which is easily cleared by the immune system, has difficulty penetrating complex tumor matrixes, and suffers from complex synthesis methods and high costs; it also addresses the issues of insufficient rigidity, instability, inability to accurately reach tumor sites, and limited functionality in existing single-membrane structures. The method comprises: 1. Dispersing a thylakoid membrane in pure water, then heating and adding hydrochloric acid solution to obtain a Mg-removed Nks system; 2. Adding an aqueous manganese chloride solution to the Mg-removed Nks system, then adjusting the pH and continuing stirring. This invention is used for the preparation of biomimetic nanocomposite materials based on thylakoid membranes.