42 results about "Tumor stroma" patented technology

The invention relates to a single chimeric converter for a T-cell signal and application thereof, which belongs to the fields of molecular biology and immunology. Specifically speaking, the single chimeric converter is formed by connection of a polypeptide highly efficiently bonding with immunosuppression molecules on the surfaces of tumor cells and / or tumor matrix cells to a transmembrane domain originated from a high-affinity receptor and an intracellular peptide fragment of a costimulatory signal molecule through a hinge structure. Out-membrane polypeptide receives a signal of the immunosuppression molecules on the surfaces of tumor cells and / or tumor matrix cells and transmits the signal into a cell, a second signal of immune cells is activated through the intracellular peptide fragment of the costimulatory signal molecule, so multiplication capacity of the immune cells and the secretion function of cell factors are enhanced, and the survival time of the activated immune cells is prolonged; thus, side-effects of a tumor immunosuppression microenvironment on adoptive cell therapy effector cells are overcome.

The present invention provides a method of treating cancer by providing to a subject in need thereof an immunogenic composition comprising a nucleic acid construct encoding a polypeptide comprising CTL epitopes PSMA288-297 and PRAME425-433, or a cross-reactive analogue. In embodiments of the present invention there is provided methods and compositions for inducing, entraining, and / or amplifying the immune response to MHC class-I restricted epitopes of carcinoma antigens to generate an effective anti-cancer immune response.

The present invention provides methods for the generation of xenochimaeric animals; for example, xenochimaeric mice, comprising bone marrow progenitor cells and tumors from a heterologous animal. In some aspects, the invention provides xenochimaeric mice bearing humanized bone marrow and human tumors. Such animals are a model system for the study of human tumor stroma, for drug discovery, and for the treatment of human cancers.

This invention provides a method for treating a subject afflicted with a tumor using genetically modified mesenchymal stem cells, wherein each genetically modified mesenchymal stem cell contains an exogenous nucleic acid comprising (i) a cytotoxic protein-encoding region operably linked to (ii) a promoter or promoter / enhancer combination, whereby the cytotoxic protein is selectively expressed when the genetically modified mesenchymal stem cells come into proximity with the tumor's stromal tissue. This invention further provides genetically modified mesenchymal stem cells for use in this method.

The invention discloses a tumor stroma pH sensitive target dendrimer and a preparation method thereof. The general formula of the dendrimer is CMCS-PAMAM-X, wherein CMCS is carboxymethyl chitosan, PAMAM is a fifth generation positive ion polyamide-amine dendritic polymer and X is adriamycin. The preparation method sequentially comprises the following three steps: preparing the CMCS; preparing a drug-loading PAMAM inner core; and preparing the pH sensitive target dendrimer. The dendrimer disclosed by the invention not only realizes targeted delivery of drugs to the tumor tissues and reduces the toxic and side effects of a tumor target drug-loading delivery system on normal tissues, but also further promotes transfer of carrier cross tumor cell membranes, so that accumulation of the drug in the tumor cells is increased, thereby improving the curative effect.

The invention discloses medicine-carried mesoporous silica coated polypyrrole nanoparticles and a preparation method thereof. The preparation method comprises preparation of polypyrrole nanoparticlesand preparation of the medicine-carried mesoporous silica coated polypyrrole nanoparticles. The medicine-carried mesoporous silica coated polypyrrole nanoparticles prepared by the preparation method disclosed by the invention are simple in preparation process, low in production cost and easy in industrial production. On the one hand, the novel nano preparation enters the tumor stroma through an EPR (Enhanced Permeability and Retention) effect of a tumor site to realize passive targeted drug delivery of the tumor, thereby improving the bioavailability of the drug, reducing the toxic and side effects of the drug and enhancing the therapeutic action of the drug; and on the other hand, polypyrrole coated in the novel nano preparation has very high photothermal conversion efficiency, so that the novel nano preparation can simultaneously perform photothermal therapy and realize photoacoustic imaging and has potential clinical application values.

The invention belongs to the fields of molecular biology and immunology, and relates to chimeric chemokines receptors capable of making T cells tend to tumor locations. Specifically, the chimeric chemokines receptors are formed in a manner that a peptide fragment of a generated factor secreted by efficiently-combined tumor cells or tumor stromal cells is connected with a transmembrane region originated from a high-affinity receptor and a signal domain peptide fragment capable of making the T cells efficiently migrated through hinge structures. A membrane outer peptide fragment receives a corresponding factor signal and transfers the signal into cells, and a related path for promoting T cell chemotaxis is started through an intracellular region of the signal domain peptide fragment capable of promoting the migration of the T cells, so that the T cells modified by the chimeric chemokines receptors have a characteristic of migrating to the corresponding factor high concentration direction, and a normal tumor killing activity is not weaken, so as to ensure the tumor adoptive cell therapy effector T cells can efficiently reach the tumor nidus locations, and play a role in treatment.

The present invention includes compositions and methods for the treatment of cancers by controlling the type of immune response mounted against the tumor, and more particularly, the treatment of tumors with cytokine antagonists to change the type of helper T cell response and inhibition of angiogenesis, prevention of formation of metastasis and prevention of formation of tumor stroma.

A method for altering the composition of tumor infiltrating mononuclear cells, increasing CD4+ / CD8+ ratio, increasing tumor stroma / epithelial ratio and modulating HLA (Human Leukocyte Antigen) class II expression on a tumor cell surface with a serum-free and mitogen-free mixture having specific cytokine ratios from the group of IL-1β, TNF-α, IFN-γ, GM-CSF, and Interleukin-2 (IL-2) with specific ratios of IL-1β, TNF-α, IFN-γ, GM-CSF to IL-2, respectively. The serum-free and mitogen-free mixtures comprised of cytokine ratios include Leukocyte Interleukin Injection (LI) or Multikine®, which can be further used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.

The invention discloses a polypeptide combined with an FAP (Fibroblast Activation Protein). The polypeptide is obtained by screening from a phage display peptide library, can be specifically combined with the FAP, has high activity and has a sequence of SCDYNHHWC. The polypeptide can be used for preparing a broad spectrum probe aiming at a tumor matrix, and can meet the application requirement on the aspects of molecular imaging of tumors, targeting therapy of tumors, and the like.

A DNA composition effective for eliciting an immune response against tumor cells and tumor metastases comprising a DNA construct that encodes for at least one epitope of fibroblast activation protein (FAP), which is expressible in immune cells, and which is incorporated in a pharmaceutically acceptable carrier. The composition can encode a single epitope of FAP, a polypeptide comprising two or more epitopes of FAP, the entire FAP protein, or any portion thereof that will elicit the desired immune response. In one preferred embodiment, the composition also includes a DNA construct that encodes an immune effector protein, such as a cytokine. The DNA composition of the invention can be used alone or in combination with a chemotherapeutic agent to treat diseases such as tumors and tumor metastases.

The invention discloses a use of third-valence metal salt as MMPs inhibitor, the third-valence metal salt is free third-valence metal salt or third-valence metal composition. The third-valence metal salt is third-valence rare earth salt or third-valence transition metal salt or third-valence major-group metal salt. Compared with prior MMPs inhibitor, the third-valence metal salt of the invention has relatively strong MMPs inhibiting activity; furthermore, the third-valence metal salt of the invention has simple structure, low cost and convenient availability.

A method of treatment of cancer with a formulation of liposomally encapsulated glutathione, that is preferably used orally, increases the level of glutathione in tissues in order to prevent and reverse the metabolic changes in cells that results in the formation of the metabolic “fuel supply” that supports cancer cells, and without which the cells can die out. The method prevents the oxidative stress that damages normal support cells such as stromal fibroblast cells. By blocking the “fuel supply,” the invention can protect, prevent and reverse these cells from the steps of autophagy and mitophagy, that results in the cells decreasing the normal production of ATP for energy and using aerobic glycolysis for energy production. The use of oral liposomally encapsulated glutathione will maintain the presence and normal function of caveolin in fibroblast and other cells, thus preventing their conversion to autophagic tumor stromal cells.

The invention discloses a bionic exosome as well as preparation and application thereof. An artificial lipid material is subjected to tumor cell membrane protein chimerism to prepare a nano-liposome with a particle size similar to that of an exosome structure, and NE is combined on the surface of the nano-liposome through electrostatic adsorption so as to be used as the bionic exosome. The bionicexosome has a stable lipid membrane structure, tumor targeting and a tumor matrix degradation function. After the bionic exosome degrades a tumor matrix in a targeting manner, the permeation of an anti-cancer drug into a tumor and the immersion of immune cells into the tumor can be enhanced, the anti-tumor curative effect is greatly improved, and the bionic exosome has huge conversion value and application prospect in the aspect of combined chemotherapy / immune anti-tumor.

A DNA composition effective for eliciting an immune response against tumor cells and tumor metastases comprising a DNA construct that encodes for at least one epitope of fibroblast activation protein (FAP), which is expressible in immune cells, and which is incorporated in a pharmaceutically acceptable carrier. The composition can encode a single epitope of FAP, a polypeptide comprising two or more epitopes of FAP, the entire FAP protein, or any portion thereof that will elicit the desired immune response. In one preferred embodiment, the composition also includes a DNA construct that encodes an immune effector protein, such as a cytokine. The DNA composition of the invention can be used alone or in combination with a chemotherapeutic agent to treat diseases such as tumors and tumor metastases.

A method for altering the composition of tumor infiltrating mononuclear cells, increasing CD4+ / CD8+ ratio, increasing tumor stroma / epithelial ratio and modulating HLA (Human Leukocyte Antigen) class II expression on a tumor cell surface with a serum-free and mitogen-free mixture having specific cytokine ratios from the group of IL-1β, TNF-α, IFN-γ, GM-CSF, and Interleukin-2 (IL-2) with specific ratios of IL-1β, TNF-α, IFN-γ, GM-CSF to IL-2, respectively. The serum-free and mitogen-free mixtures comprised of cytokine ratios include Leukocyte Interleukin Injection (LI) or Multikine®, which can be further used alone or in combination with other drugs for the treatment of cancer thereby increasing the success of cancer treatment and the disease free survival of cancer patients.

The invention relates to a compound phospholipid thermosensitive lipidosome with an effect of simultaneously delivering drugs in double target areas, a preparation method and an application thereof. According to the invention, a folic acid modified cyclodextrin loaded drug is used for preparing an inclusion compound, and then the folic acid modified cyclodextrin inclusion compound and free drugs are respectively loaded into an inner water phase and a lipid bilayer of a compound phospholipid thermosensitive lipidosome; in an antitumor application, the free drugs and the drug-loading folic acid modified cyclodextrin inclusion compound are triggered to release from the lipidosome on a target part in the manner of heating; the free drugs mainly act on the tumor extracellular mesenchyme; the folic acid modified cyclodextrin inclusion compound enters tumor cells in the manner of receptor-mediated active targeting drug delivery; the simultaneous drug delivery in the tumor stroma and tumor cell double target areas is finally realized; the optimal therapeutic effect is realized in the manner of flexibly adjusting the drug ratio in the free drugs and the folic acid modified cyclodextrin inclusion compound. The invention is especially suitable for the antitumor application of complex component or monomer component of the traditional Chinese medicine with multiple effects and has wide application prospect in the aspect of research on a novel antitumor drug delivery system.

The invention discloses a group of colon cancer metastasis related tumor stroma markers. The group of marks exist in a tumor stroma, and marker expression abnormality is also more obvious along with the development of canceration, wherein one marker Tenascin-C belongs to a novel extracellular matrix marker, generates abnormal expression in the early stage of tumor canceration, and also generates abnormal expression in a metastasis position, wherein the marker for the self secretion of a tumor is relevant to the metastasis capability. The group of markers can be used for preparing medicines and a kit for colon cancer metastasis screening and auxiliary diagnosis.

The invention provides a pharmaceutical composition for mild photothermal therapy of tumors as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition is composed of a dual-targeting amphiphilic glucan derivative carrier, a material (PTA) with photo-thermal conversion performance and an autophagy inhibitor. The dual-targeting amphiphilic glucan derivative carrier can be self-assembled in water to form nano-micelles, and is physically loaded with PTA and an autophagy inhibitor for tumor photothermal therapy. The preparation is mainly characterized in that: 1) the preparation has active dual-targeting capability of tumor cells and tumor-related fibroblasts, and can efficiently enter the cells through the action of receptor ligands, so that the transfer efficiency of the preparation is improved; 2) under the irradiation of 808nm laser, PTA absorbs light energy and efficiently converts the light energy into heat, and the autophagy inhibitor inhibits the autophagy behavior of tumor cells and sensibilizes photo-thermal, so that an excellent mild photo-thermal treatment effect is realized, and the physical barrier of a tumor matrix can be weakened; tumor photothermal can further induce tumor cells to generate immunogenic cell death, generated tumor fragments can further activate an immune system, and the tumor photothermal treatment effect is greatly improved.

The invention provides an amphiphilic dextran derivative carrier for targeting tumor-associated fibroblasts and preparation and application of a pharmaceutical composition of the amphiphilic dextran derivative carrier. The amphiphilic dextran derivative carrier comprises a derivative skeleton modified by hydrophilic dextran carboxyl, an FAP-alpha responsive peptide fragment connecting arm and a hydrophobic group molecule. The amphiphilic derivative is self-assembled in an aqueous solution to form nanoparticles, and molecules with pharmacological activity can be physically loaded for tumor treatment. The amphiphilic dextran derivative carrier is mainly characterized in that: (1) after the nanoparticles reach a focus part, a specific peptide fragment connecting arm can be subjected to enzyme digestion by FAP-alpha which is specifically and highly expressed on the surface of tumor-associated fibroblasts, so that the nanoparticles are rapidly degraded; and (2) the pharmacological active molecules which are physically loaded are quickly released from the disintegrated nanoparticles, tumor-associated fibroblasts can be effectively killed or the function thereof can be inhibited, the physical barrier of a tumor matrix can be weakened, and the permeation of an anti-tumor preparation can be promoted when the nano-particles are combined with other anti-tumor preparations, so that the treatment effect of the anti-tumor preparation can be effectively improved.

The invention discloses a size-variable intelligent drug-loading nano-cluster system and a preparation method and application thereof. The drug-loaded nano-cluster is composed of an outer-layer reticular host carrier with good biocompatibility and an inner small-size parasitic carrier. The nano-cluster has good safety and long circulation characteristics, after being efficiently accumulated at a tumor part, the nano-cluster intelligently adjusts the size under the stimulation of a tumor microenvironment, and releases small-size drug-loaded micelles to penetrate through a compact tumor matrix to realize deep drug delivery, so that the permeability and lethality of the drug are enhanced, and the toxic and side effects are reduced. The nano-cluster is a flexible drug loading platform, and has great practical value in the field of nano-drug treatment of solid tumors.

This invention proposes an agent to block the “fuel supply” that energizes cancer cell growth by protecting surrounding cells to the cancer, particularly stromal fibroblast cells. The invention disables the products of surrounding cells useable for energy conversion by the cancer cell thereby crippling the cell and disabling its growth process. This application describes the use of a formulation of liposomally encapsulated glutathione that is preferably used orally to increase the level of glutathione in tissues in order to prevent and reverse the metabolic changes in cells that results in the formation of the metabolic fuel that supports cancer cells and to prevent the oxidative stress that damages normal support cells such as fibroblasts and can prevent and reverse these cells from the steps of autophagy and mitophagy that results in the cells decreasing the normal mitochondrial production of ATP for energy and resorting to the use of aerobic glycolysis for energy production. The use of oral liposomally encapsulated glutathione will maintain the presence and normal function of caveolin in fibroblast and other cells, thus preventing their conversion to autophagic tumor stromal cells. By stopping the formation of autophagic cells, the production of the metabolic fuel needed by cancer cells is stopped, which results in the death of the cancer cells. Compositions using liposomally encapsulated glutathione and other compounds that enhance the favorable effects of liposomal glutathione on cancer disease are referenced.

The invention belongs to the field of drugs and health-care food, and discloses a traditional Chinese medicine composition, which contains ganoderma lucidum polysaccharides, grifola frondosa polysaccharides, angelica sinensis oil and cinnamon oil. Experiments show that the prepared traditional Chinese medicine composition is scientifically combined, brings out the best in each other, has no toxic and side effects, not only has nutritional values, but also can inhibit the growth of tumors, remarkably increase the percentage of CD<4+> and CD<8+> cells in tumor stroma lymphocyte compared with single component, enhance the organism immunity function, restore the normal immune monitoring function of the organism, reduce the expression rate of mice tumor tissue VEGF and TGF-beta1 positive cells, help treat tumors, enhance the anti-tumor effect of chemotherapeutic drugs, and improve the organism immunity condition, has the function of restoring the normal immune monitoring of the organism, and can play a role in preventing and / or help treating tumors.

The invention discloses a pharmaceutical composition with a synergistic effect and myofibroblast capable of resisting organ fibrosis and tumor stroma. The pharmaceutical composition is composed of tetrandrine, a tetrandrine derivative, baicalein and a baicalein derivative, has the synergistic effect and the myofibroblast capable of resisting organ fibrosis and tumor stroma, is capable of reducing expression of myofibroblast alpha-smooth muscle actin (alpha-SMA), enables the myofibroblast alpha-smooth muscle actin (alpha-SMA) to be restored to fibroblast in resting time, and is used for treating organ fibrosis and suppressing tumor growth, metastasis and infiltration. The pharmaceutical composition has no obvious toxic or side effects on fibroblast while obviously reducing expression of alpha-SMA.

The invention belongs to the technical field of drug targeting carriers, and discloses a co-drug-loading cell microparticle preparation and a preparation method thereof, the co-drug-loading cell microparticle preparation comprises microparticles secreted from tumor cells, and a photosensitizer and a tumor-associated fibroblast deactivator together entrapped in the microparticles. The detailed composition and the structure of the preparation are improved, microparticles secreted from tumor cells are taken as carriers, and the photosensitizer and the tumor-related fibroblast deactivator are simultaneously entrapped in the carriers, so that the obtained co-drug-loading cell microparticle preparation has the advantages that on one hand, the tumor matrix microenvironment is transformed, the enrichment of the photosensitizer in tumors is enhanced, and the tumor-related fibroblast deactivator can be effectively inhibited; on the one hand, the direct killing effect of photothermal therapy on tumor cells can be improved, on the other hand, tumor immunogenic death caused by photothermal therapy can be enhanced, CD8 + T cell infiltration can be promoted, CD8 + T cell death induced by antigen-dependent activation caused by tumor-related fibroblasts can be reduced, and the tumor immune microenvironment can be improved.