110 results about "Tumor-associated macrophage" patented technology

Macrophages within the tumor microenvironment, also called tumor associated macrophages (TAMs) have been shown to play a major role in the growth and spread of many types of cancer. Cancer cells produce cytokines that cause the macrophages to differentiate into an M2 subtype. We have designed a mannosylated liposome (MAN-LIPs) and successfully showed it to accumulate in TAMs in a mouse model of pulmonary adenocarcinoma. These liposomes are loaded with 64Cu to allow tracking by PET imaging, and contain a fluorescent dye in the lipid bilayer permitting subsequent fluorescence microscopy. MAN-LIPs are a promising new vehicle for the delivery of imaging agents to lung TAMs. In addition to imaging, they hold the potential for delivery of therapeutic agents to the tumor microenvironment.

Methods for the treatment of cancer with therapies targeting tumor-associated macrophage activities are provided. Methods for the treatment of cancer, inflammatory and autoimmune disorders with therapies using tumor-associated macrophages and adipose tissue macrophages are also provided.

The invention relates to activities and characteristics of tumor-associated macrophages (TAMs). In particular, immunoglobulin single variable domains are provided against markers of TAMs, and methods using the same for in vivo imaging of tumor cells, as well as cancer diagnostics and therapeutics.

The invention discloses a macrophage drug-loaded MP (microparticle) preparation and a preparation method thereof. The macrophage drug-loaded MP preparation comprises cell vesicles and drug small molecule effective components wrapped in the cell vesicles, wherein the cell vesicles are released by apoptosis of mannose modified macrophages. The drug-loaded microparticles can be highly enriched in tumor tissue and more easily absorbed by M2 type tumor-related macrophages, the antipolarization effect of small molecule drugs on M2 type tumor-related macrophages is improved, the tumor microenvironment is improved, killing of tumor cells is enhanced, the problems that small molecule drugs cannot be effectively enriched or target and antipolarize M2 type tumor-related macrophages at tumor sites canbe solved, and toxic and side effects of the small molecule drugs on organisms are also reduced.

The disclosure relates to immunoglobulin single variable domains directed against human macrophage mannose receptor (MMR) and their uses in the field of oncology. More specifically, it concerns immunoglobulin single variable domains, including single-domain antibodies (sdAbs), against human MMR and their use in targeting and in vivo imaging of tumor-associated macrophages, with applications in the field of cancer diagnostics and therapeutics and monitoring of the disease.

Provided herein are compositions including particles that comprise a bisphosphonate compound and a tumor specific targeting peptide or peptidomimetic. Also provided herein are methods of reducing tumor associated macrophages and methods of treating cancer with said compositions.

The invention discloses double-target polypeptide of a tumor-associated macrophage, a nano particle, preparation and an application and relates to the technical field of bioscience and drug carriers.The double-target polypeptide is prepared by series connection of alpha helix polypeptide, a catenation sequence and M2 macrophage target peptide in a covalent bond form. The nano particle prepared bythe double-target polypeptide can perform efficient targeted transportation of drugs to the tumor-associated macrophage, so that the tumor-associated macrophage is specifically eliminated and tumor growth is inhibited; a preparation technology of the nano particle targeting to the tumor-associated macrophage is simple; large-scale production is facilitated; most raw materials for preparing the nano particle are used clinically or used in clinical experiments; and a detection result shows that no toxic or side effects are caused on physiologic and biochemical indexes of a mouse.

The invention discloses an miRNA-supported composite nanoparticle. The miRNA-supported composite nanoparticle is prepared from a cation targeted membrane material, an acid sensitivity membrane material and at least one miRNA, wherein the cation targeted membrane material is selected from a galactose-polylysine-polycysteine polymer; the acid sensitivity membrane material is selected from a polyethylene glycol-polylysine polymer of which a side chain is modified by 3,4,5,6-tetrahydrophthalic anhydride ligand; and the miRNA is selected from miRNA for inducing differentiation from tumor-associatedmacrophage to M1 type macrophage. According to the miRNA-supported composite nanoparticle disclosed by the invention, accurate delivery of the tumor-associated macrophage is realized by pH value targeting and active targeting, and the function of promoting the differentiation from the tumor-associated macrophage to the M1 type macrophage is realized.

The invention relates to a nano particle carrier having tumor and tumor-associated macrophage targeting multiple functions, which can be used for tumor therapy and in vivo imaging and positioning. The carrier is a liposome nano particle mediated by a tumor focus induction-activated cell-penetrating peptide, can be specifically enriched on the tumor focus through a circulating system after being subjected to intravenous injection, and simultaneously has the functions of molecule imaging and carrying multiple biomacromolecules and medicines. Concretely, by using a TAT cell-penetrating peptide of closed active center amino acid of a Legumain specificity-identified enzyme digestion substrate to connect PEG-modified liposome nano particles, after the circulating system reaches the tumor focus position, Legumain expressed by tumor and tumor-associated macrophage can separate the enzyme digestion substrate from the TAT active center, thereby realizing the enrichment on the tumor focus. The nano particle can pack various biomacromolecules or medicines, and has the functions of killing tumor, in vivo tumor tracing and performing early prevention on tumor.

The present invention relates to cancer immunotherapy. In particular, provided herein are fusion proteins for targeting tumor associated macrophages with immunostimulatory agents.

The present invention features methods of directly targeting specific cell surface receptors on the M2 macrophage for antibody or nanoparticle directed therapy.

The invention relates to a medicine conveying system formed by ligand polypeptide PH1 and an application thereof. The medicine conveying system comprises a ligand polypeptide PH1, a medicine carrying system and at least one active substance, wherein the polypeptide PH1 is connected on the surface of the medicine carrying system. The invention also relates to the application of the ligand polypeptide PH1 in preparing a medicine capable of specifically binding tumor-related macrophage. Discovered and proved by long-time test, the polypeptide PH1 can well target tumor-related cells, induce the differentiation of the tumor-related cells and suppress the tumor growth; the composite of PH1 polypeptide lipidosome can well target the tumor-related macrophage and can be applied to target conveying of the tumor-related macrophage of small-molecular medicines and gene medicines. The medicine conveying system has the advantages that the transretinoic acid polypeptide lipidosome can induce the differentiation of the tumor-related macrophage and suppress the tumor growth effectively, and can be applied to inhibiting proliferation of the tumor cells and the neoplasm recurrence so as to have great medical practicability.

The invention provides a tumor-targeting novel polypeptide, which is a tandem polypeptide that can target not only tumor cells and blood vessels but also tumor-related macrophages to adjust the tumor microenvironment and enhance the anti-tumor effect. Peptide substrates (AAN) which target tumor blood vessels and tumor cells, contain RGD polypeptides and targeted tumor-related macrophages and are sensitive to aspartic acid endoproteinase are connected to form the polypeptide (nRGD). The polypeptide (nRGD) not only can be applied to be directly used along with drugs or vectors, but also can modify the prodrugs of anti-tumor drugs or modify drug delivery vectors, and can effectively mediate tumor-targeting delivery, thus greatly enhancing curative effect.

The invention relates to a traditional Chinese medicine-magnetic nanocluster chemical immunity drug delivery system and a preparation method thereof. The traditional Chinese medicine-magnetic nanocluster chemical immunity drug delivery system comprises superparamagnetic oxide nanoparticles, wherein the surface of each superparamagnetic oxide nanoparticle is anchored with a drug and a TAMs (tumor-associated macrophage) targeting ligand; the superparamagnetic oxide nanoparticles form a nanocluster structure through disulfide bonds; the nanocluster structure is externally packaged with protein. The traditional Chinese medicine-magnetic nanocluster chemical immunity drug delivery system has the advantages that the target finding advantages of magnetic trend, ligand modifying and reductive sensitization are integrated; the in-vivo circulation is stable, the tumor aggregation efficiency is high, and the TAMs targeting is precise.

The invention discloses a specific DNA aptamer for a CD4 positive cell and a chimera of the specific DNA aptamer. The specific DNA aptamer is characterized in that an aptamer technology with a cell orienting function is combined with an RNAi technology to construct the specific DNA aptamer for the CD4 positive cell, so as to carry anticancer siRNA to be selectively imported into a CD4 positive tumor-associated macrophage. The function of the specific DNA aptamer for the CD4 positive cell as a vector oriented tool for delivering the anticancer siRNA and an antitumor effect are detected in an invitro tumor-associated macrophage and breast cancer cell culture system. The specific DNA aptamer and the chimera thereof disclosed by the invention are based on a novel gene anticancer drug for oriented RNAi and provide a novel idea for RNAi targeting import into target cells.

The invention provides a drug delivering miRNA for suppressing tumor growth by targeting tumor-associated macrophages and application. The drug comprises a drug carrier targeting the tumor-associatedmacrophages, miRNA wrapped in the drug carrier and cationized polysaccharide with mannose residues. The sequences of the miRNA are as shown in SEQ. ID. NO. 1 or SEQ. ID. NO. 2. Through an in vitro experiment, miR-99b-5p which can promote M1 type activation of the macrophages and can inhibit M2 type activation of the macrophages is discovered, nano-material targeting tumor-associated macrophages (TAMs) is used for wrapping the miRNA, and the wrapped miRNA is directly transported to a mouse model of liver cancer through a tail vein, it is found that delivery of the miRNA to the targeted TAMs cansignificantly inhibit tumor growth, and delivery of the miR-99b-5p to the targeted TAMs has a better effect of inhibitory action on tumor growth than delivery of other miRNAs, such as miR-125a.

The invention belongs to the technical field of medicines, and particularly relates to an immune targeting functional liposome as well as a preparation method and application thereof. The functional liposome disclosed by the invention is a blank liposome which does not entrap a drug, a membrane material contains carbohydrate ligand modified PEGylated phospholipid, the average particle size is 50-500nm, and the functional liposome has a targeting function on immunosuppressive cells in a tumor microenvironment and can promote tumor-associated macrophages to differentiate into M1 type macrophages; the polypeptide has a certain capacity of inhibiting tumor growth, can be used as an adjuvant of a tumor immune treatment, and can also be used as an entrapped delivery tool of an immunomodulator oran anti-tumor drug.

The present invention relates to a pharmaceutical composition that is anticancer and suppresses cancer metastasis, containing a fusion peptide as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition exhibiting an excellent anticancer effect and an cancer metastasis suppression effect by simultaneously targeting a cancer cell and a tumor associated macrophage (TAM) in which IL-4 receptors are over-expressed. The pharmaceutical composition of the present invention simultaneously targets a tumor cell and a TAM and kills the cells, thereby simultaneously having an anticancer effect and a cancer metastasis suppression effect. In addition, the fusion peptide of the present invention decreases side effects of conventional anticancer drugs and exhibits anticancer and cancer metastasis suppression effects, when co-administered with conventional anticancer drugs.

The invention relates to activities and characteristics of tumor-associated macrophages (TAMs). In particular, immunoglobulin single variable domains are provided against markers of TAMs, and methods using the same for in vivo imaging of tumor cells, as well as cancer diagnostics and therapeutics.

The invention relates to a lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as a preparation method and application thereof. The lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages disclosed by the invention takes lipids as a shell membrane material, and wraps low-molecular-weight hyaluronic acids and gaseous fluorocarbon in the shell membrane; and the lipids consist of dipalmitoyl-phosphatidylcholine (DPPC), distearoyl-phosphatidylethanolamine (DSPE) and distearyl phosphatidylethanolamine-polyethylene glycol-folic acids (DSPE-PEG-FOL). The lipid nano-scale ultrasound contrast agent has a particle size of 255-497 nm, and is capable of passing through vascular wall space of tumor tissue so as to achieve tumortreatment effects with passive targeting and high efficiency; PEG chain is utilized so as to have coupled folic acids located outside the lipids shell membrane and the low-molecular-weight hyaluronicacids wrapped in the contrast agent, so that it is ensured that the lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages can actively target the tumor-associatedmacrophages by a folic acid-folic acid receptor way; and the low-molecular-weight hyaluronic acids act on the tumor-associated macrophages, so that the tumor-associated macrophages can be transformedfrom type-M2 macrophages into type-M1 macrophages.

The invention relates to a use of an miR-100 inhibitor in cancer metastasis reduction, and concretely relates to a use of a reagent for determining the miR-100 expression level in the preparation of breast cancer diagnosis reagents, and a use of the miR-100 inhibitor, and a use of the miR-100 inhibitor or an miR-100 antagonist in the preparation of medicines for treating breast cancer. Up-regulation of miR-100 in in-vivo tumor related macrophages and in-vitro induced M2 type macrophages is induced by tumor micro-environment. In in-vivo test, the microRNA antagonist knocks down the expression of the miR-100 in mouse mammary gland tumor tissues, and a case that in-situ tumor growth has no statistic difference, the quantity of lung metastasis tubercles is obviously down-regulated and the mammary gland tumor metastasis is inhibited in an experiment group of the miR-100 down-regulation in the tumor related macrophages is found.

The invention provides an M1 type macrophage exosome vaccine as well as a preparation method and application thereof. The M1 type macrophage exosome vaccine is characterized in that an exosome vaccine M1Ag-Exos is obtained by enabling M1 type macrophages to uptake a specific tumor antigen Ag and then extracting an exosome of the M1 type macrophages carrying the tumor antigen Ag. According to the M1 type macrophage exosome vaccine, the exosome vaccine capable of adjusting the tumor immune microenvironment is constructed to enhance the immunotherapy efficiency, and polarization of tumor-related macrophages and the remarkable immune activation effect of a tumor vaccine are achieved through the M1 type macrophage exosome; the tumor-related macrophages are polarized into M1 type, so that the macrophages are converted from a state of promoting tumor invasion and metastasis by immunosuppression into a state of supporting tumors by immunity; meanwhile, through immunoregulation on the tumor microenvironment, the tumor vaccine can promote proliferation and activation of T cells more efficiently, and growth and metastasis of the tumors are effectively inhibited.

The invention discloses application of a paeoniflorin derivative CP-25. The application refers to application in preparation of a pharmaceutical preparation for treating human brain glioma. The structural formula of the paeoniflorin derivative CP-25 is as shown in the specification. The paeoniflorin derivative CP-25 disclsoed by the invention is capable of achieving an effect of inhibiting gliomaoccurrence and development by inhibiting tumor-associated macrophage mediated angiogenesis, and can be prepared into injection, tablets, capsules, dropping pills, granules and the like.

A cancer vaccine technology is provided which knocks out expression of cell surface immune checkpoint proteins, to facilitate their processing by immune cells, and optionally by knocking-in the expression of cytokines to boost immune response. Non-replicating tumor cells lacking cell surface CD47 are highly effective immunizing agents against subcutaneous mouse melanoma. Whole-cell vaccines inhibited tumor growth, and immunophenotyping showed a dramatic increase in activated effector cell subsets and M1-type macrophages aided by a significant reduction in the tumor-associated macrophage and myeloid derived suppressor cell compartments. A remarkable downregulation of cell surface CD47 was observed in the tumors that did escape after vaccination with genetically modified cells, suggesting the intricate involvement of CD47 in a prophylactic situation. An effective vaccination strategy to increase tumor-specific immune response in solid tumors is provided to improve the outcome of cancer immunotherapy.

Methods for treating cancers using one or more compounds comprising a folate receptor binding ligand attached to a drug via a linker are described. Methods for treating cancers using one or more compounds comprising a folate receptor binding ligand attached to a drug via a linker to target tumor associated macrophages are described.

The present invention discloses a tumor immunotherapy target aiming at tumor-associated macrophages. Experiments prove that LSECtin, BTN3A2 and BNT3A3 can promote tumor progression by promoting of thestemness maintenance of tumor cells, more specifically, formation of tumor cell spheres, expression of stem transcription factors and tumor progression in a mice tumor model are promoted; by inhibition of interaction of the LSECtin with the BTN3A2 and the BTN3A3, the tumor progression can be effectively slowed down, more specifically, the incidence of tumors is reduced, and tumor volume growth can be slowed down.

The invention relates to calcium carbonate based compound micro particles and preparation and application thereof. The calcium carbonate based compound micro particles disclosed by the invention comprise calcium carbonate and a macromolecule stable layer, wherein the macromolecule stable layer comprises amphipathic molecules and / or hydrophilic molecules. The invention further discloses applicationof the calcium carbonate based compound micro particles to preparation of one or more of an adjuvant, a chemotherapy enhancing adjuvant, a radiotherapy enhancing adjuvant and a radiofrequency ablation treatment adjuvant for tumor immnuotherapy. The calcium carbonate based compound micro particles disclosed by the invention have an excellent effect of regulating a tumor slight acid environment, can reduce content of immunosuppressive cells in tumor, increase content of immune cells capable of killing the tumor and promote polarization of tumor-associated macrophages from the M2 type to the M1type, effectively turns the tumor immunosuppression micro environment, activate antitumor immunity, and can enhance a suppression effect of various treatment means of immunotherapy, chemotherapy, radiotherapy, radiofrequency ablation treatment and the like on tumor growth.

The invention relates to the field of biological medicine, in particular to application of PPAR gamma to influence liver cancer by promoting terminal differentiation of MMP9 <+> tumor-associated macrophages. Research results show that the proportion of MMP9+ TAMs in liver cancer tissues is increased and is significantly related to poor prognosis of patients; further experimental results show that PPAR gamma promotes deterioration of liver cancer by inducing differentiation of MMP9 + TAMs; after the PPAR gamma is knocked down or knocked out, the proportion of inducing THP1 cells into MMP9 + TAMs is reduced, and after the PPAR gamma is knocked down or knocked out, the proportion of inducing PBMC cells into MMP9 + TAMs is reduced; after THP1 cells of which PPAR gamma is knocked down or knocked out are induced into TAMs, the migration, invasion and tube forming capabilities of liver cancer cells are reduced; and after the PBMC with the PPAR gamma knocked down or knocked out is induced into TAMs, the migration, invasion and tube forming capabilities of the liver cancer cells are reduced.

The invention relates to an immune escape nano preparation, and belongs to the technical field of biological medicines. The immune escape nano-preparation comprises a nano-micelle and an antitumor drug entrapped in the nano-micelle, the nano-micelle is formed by connecting polypeptide MSP and a micelle material Mal-PEG-PCL, the polypeptide MSP is designed based on a crystal structure in which beta 2M and LILRB1 interact, the amino acid sequence of the polypeptide MSP is Cys-GPLGVRGTLSQPKIVKWDRDM, and after the polypeptide MSP is coupled with Mal-PEG-PCL, the polypeptide MSP and the micelle material Mal-PEG-PCL are coupled to form the nano-micelle. The nano-micelle capable of actively escaping macrophage phagocytosis can be formed, an anti-tumor drug is entrapped in the nano-micelle to obtain the immune escape nano-preparation, and the nano-preparation can actively escape macrophage phagocytosis and can be taken by tumor-related macrophages.