66 results about "Macrophage targeting" patented technology

The invention belongs to the technical field of genetic engineering and biological medicine, and particularly discloses a cascade response type nano-particle with a microenvironment remodeling function and a preparation method and application of the cascade response type nano-particle. The nanoparticle provided by the invention adopts a bionic hybrid membrane engineering strategy: an inner core is formed by loading an exosome inhibitor on a nano material, and the surface is covalently coupled with M2 type macrophage specific targeting peptide; the outer layer coats a macrophage membrane and active oxygen response type liposome composite membrane layer through a co-extrusion technology, and is loaded with a TLR agonist. Animal experiments show that after being injected through caudal vein, the nano-particles are enriched at a tumor site in a targeted manner through homing receptors such as membrane surface integrin alpha4beta1 and the like, and outer membrane cracking is triggered in a high-ROS tumor microenvironment, so that space-time controlled release of a TLR agonist and targeted phagocytosis of an exosome inhibitor by macrophages guided by a targeted peptide are realized. The anti-tumor synergistic effect is achieved through multiple regulation and control mechanisms, and an effective treatment strategy is provided for tumor immunotherapy.

The invention discloses a step-by-step targeting placenta trophoblast micro-nano robot as well as a preparation method and application thereof. The micro-nano robot comprises a yeast cell wall of a bag-shaped structure, bio-enzyme unevenly distributed on the surface of the yeast cell wall and targeted placenta trophoblast drug-loaded nanoparticles located in the yeast cell wall. The surfaces of the targeted placenta trophoblast drug-loaded nanoparticles are connected with placenta-like chondroitin sulfate A binding polypeptides. Inflammation placenta tissue can be targeted through macrophages, the medicine is accurately delivered to placenta trophoblastic cells through the medicine-carrying nano-particles connected with the targeting peptide, step-by-step accurate targeting is achieved, the medicine does not penetrate through the placenta barrier to reach the body of a fetus, and high biological safety is achieved for pregnancy administration.

The invention discloses bioactive macroporous hydrogel as well as a preparation method and application thereof. The bioactive macroporous hydrogel comprises hydrogel particles and a bioactive load loaded on the hydrogel particles, the hydrogel particles are obtained by mechanically extruding a hydrogel matrix, and the hydrogel matrix is formed by compounding sodium alginate, agarose and methacrylated hyaluronic acid through hydrogen bond crosslinking and photo-crosslinking; the bioactive load comprises: a) small extracellular vesicles of which the surfaces are modified with macrophage targeted CRV peptides; and b) a PLGA (poly (lactic-co-glycolic acid)) microsphere loaded with a cartilage inducer Kartogenin. The bioactive macroporous hydrogel disclosed by the invention has an internally communicated macroporous network, is beneficial to cell infiltration, blood vessel ingrowth and nutrient substance diffusion, and overcomes the defects that the traditional hydrogel is small in pore size and limits cell behaviors. According to the bioactive macroporous hydrogel disclosed by the invention, dual bioactive loads are adopted to synergistically promote tendon-bone healing, so that the treatment effect is better.

The invention discloses a preparation method of macrophage targeting ASD nano particles, a prepared nano carrier and application of the nano carrier, ASD active molecules can be controllably released under the stimulation of an intracellular microenvironment (high ROS and low pH), inflammation is eliminated, meanwhile, lipid efflux is increased, and therefore effective intervention on atherosclerosis is achieved. The method comprises the following steps: (1) synthesizing a 3-acrylamido phenylboronic acid monomer B; (2) synthesizing a phenylboronic acid polymer pB; (3) synthesizing a conjugate PB-ASD of a phenylboronic acid polymer pB and akebiaquinata saponin D; (4) synthesizing a mannose modified polymer Man-PEG (Polyethylene Glycol)-DSPE (Distearoyl Sulfonate And (5) blending the Man-PEG-DSPE and the conjugate PB-ASD, and preparing the macrophage targeting ASD nano particle ASD (at) DPM NPs in an oil / water system, so as to obtain the macrophage targeting ASD nano particle ASD (at) DPM NPs.

The present invention belongs to the field of biotechnology and pharmaceutical engineering technology, and discloses a functionalized drug-loaded exosome based on milk exosomes, a preparation method thereof, and an application thereof. The functionalized drug-loaded exosomes include a carrier and a water-insoluble drug, and the water-insoluble drug is loaded inside the carrier; wherein the surface of the carrier is loaded with milk exosomes with functionalized molecules, and the functionalized molecule is any one of phosphatidylserine, a molecule capable of macrophage targeting, and a molecule or polymer that enhances the targeting and stability of milk exosomes; the water-insoluble drug is any one of an antibacterial drug, an antitumor drug, and a gene drug. The functionalized drug-loaded exosomes in the present invention can improve the gastrointestinal stability of oral administration and enhance the efficacy against bacterial pathogens; expand the application scope of milk exosomes in the fields of anti-intestinal bacterial infection and food preservation, and the exosome content in milk is very rich, which is convenient for large-scale preparation and has important application value.

The invention discloses an anti-inflammatory CAR-macrophage targeting FAP, a preparation method thereof and application of the anti-inflammatory CAR-macrophage in preparation of drugs for treating fibrosis diseases, and belongs to the technical field of biological medicines. The invention provides an FAP-specific chimeric antigen receptor, an mRNA expression vector of the FAP-specific chimeric antigen receptor, a His-labeled STING signal channel inhibitor and an mRNA expression vector of the His-labeled STING signal channel inhibitor. In-vivo and in-vitro macrophage editing can be effectively realized by delivering CAR mRNA and TRIM13mNRA through LNP, the ability of targeted phagocytosis of FAP positive cells is endowed, meanwhile, anti-inflammatory phenotypic polarization of macrophages is promoted, local inflammation is improved, and fibrosis progress driven by inflammation is synergistically restrained.

The invention provides a mesoporous bioactive glass hybrid material and a preparation method and application thereof, and relates to the technical field of biomedical materials.According to the method, through a multi-step reaction method, a silane coupling agent and epsilon-polylysine are used as connecting molecules, and the mesoporous bioactive glass hybrid material is prepared. A mesoporous bioactive glass hybrid material with macrophage targeting, immunoregulation and bone regeneration functions is prepared, and the hybrid material can target macrophages, regulate and control the polarization state of the macrophages to be converted from a proinflammatory phenotype to an anti-inflammatory phenotype, enhance the bone immunoregulation ability and improve the bone regeneration effect. And the material shows excellent osteogenic induction performance in an in-vitro experiment, and a new thought is provided for research and development of bone repair materials. The method adopted by the invention is simple and easy to implement, and the prepared mesoporous bioglass hybrid material has good application potential in bone immunoregulation and bone tissue repair.

The invention discloses an inflammatory environment macrophage targeting small activation nucleic acid nano-drug as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The inflammatory environment macrophage targeting small activation nucleic acid nano-drug provided by the invention is composed of a small activation nucleic acid core and a liposome shell. After the inflammatory environment macrophage targeting small activation nucleic acid nano-drug is actively targeted to an inflammatory environment and enters cells through receptor recognition, a liposome coat is swelled and disintegrated, small activation RNA is released, gene expression is regulated and controlled, M1 type macrophages are reprogrammed into M2 type macrophages from the two aspects of phenotype and metabolic mode, anti-inflammatory factors are released, and the anti-inflammatory effect is achieved. The aim of inhibiting inflammation is fulfilled. Therefore, the invention has a very wide application prospect in gene therapy and immunotherapy of inflammation, infectious diseases and the like.

The invention discloses an application of a tumor-associated macrophage targeting nanoprobe in ultrasensitive magnetic resonance molecular imaging of in-vivo in-situ lung cancer. The tumor-associated macrophage targeting nanoprobe prepared by the method provided by the invention is loaded with water-insoluble supramolecular celopphane, so that Xe'molecular cage 'celopphane can be uniformly dispersed in water and a biological system, and is used for in-vivo hyperpolarized 129Xe magnetic resonance imaging. According to the nanoprobe, mannose modification is carried out on the surface of the nanoprobe, so that the nanoprobe can effectively target tumor-related macrophages in a tumor area, and targeted detection of in-situ lung cancer tumors is realized; the surface of the nanoprobe is subjected to near-infrared fluorescence molecular modification, so that fluorescence / magnetic resonance bimodal detection of solid tumors can be realized. In combination with the advantage that local drug concentration can be improved by pulmonary drug delivery, a strong 129Xe magnetic resonance signal of the developed probe can be directly detected in vivo, and in-vivo 129Xe magnetic resonance molecular imaging is realized on an in-situ lung cancer model mouse through a direct sampling imaging mode.

The invention discloses a coupling molecule with an effect of promoting macrophages to selectively swallow extracellular goods as well as a preparation method and application of the coupling molecule, and belongs to the technical field of biological medicines. The coupling molecule disclosed by the invention is a double-targeting polypeptide and consists of a macrophage targeting peptide fragment, a linker and a target cell targeting peptide fragment, wherein the target cell targeting peptide fragment comprises peptide fragments targeting tumor cells and apoptotic cells. One end of the dual-targeting polypeptide is connected with macrophages, the other end of the dual-targeting polypeptide is connected with tumor cells / apoptotic cells, and the interaction between the macrophages and the tumor cells / apoptotic cells is improved in a molecular glue mode. Aiming at tumor cells, the dual-targeting polypeptide can enhance the phagocytosis and killing effects of macrophages on the tumor cells under the action of a CD47 antibody, so that the anti-tumor effect is achieved; aiming at apoptotic cells, the dual-targeting polypeptide can promote the interplant effect of macrophages, so that the anti-inflammatory effect is achieved. Therefore, the dual-targeting polypeptide disclosed by the invention has relatively good drug development potential.

Compositions for downregulating Zeb2 in macrophages are provided. Accordingly, there is provided a composition comprising an agent capable of downregulating expression and / or activity of Zeb2 attached to a macrophage-targeting moiety or encapsulated in a particle comprising a macrophage-targeting moiety. Also provided are methods of prognosing and treating an inflammatory disease.

The invention belongs to the technical field of bioengineering, and provides a drug-loaded targeted nano platform for targeted delivery of ZIF-8 drug-loaded nanoparticles by macrophages, a preparation method and an application, aiming at the technical problem that complications are easily caused by the existing treatment means of endometriosis, so that the invention provides a drug-loaded targeted nano platform for targeted delivery of ZIF-8 drug-loaded nanoparticles by macrophages, and a preparation method and application of the drug-loaded targeted nano platform. According to the invention, the ZIF-8 nano-particles and the drugs aiming at the energy metabolism level are combined to be used as the carrier, so that endometriosis cells with acidic cell microenvironment can be targeted, drug controlled release can be realized in the acidic environment of lesions, and the effective uptake of the endometriosis cells to the drugs is enhanced, thereby effectively increasing the uptake rate and the drug concentration at the target position, and improving the curative effect of the drug on the endometriosis cells. Meanwhile, the distribution of the medicine in normal tissues or cells is reduced, and the toxic and side effects of the medicine are reduced; and through the design of combining the macrophages with the ZIF-8 nano-particle carrier, the drug targeting property of the ZIF-8 nano-particle carrier can be obviously improved.

The invention discloses a si-TGM2-loaded macrophage targeting nano-material as well as a preparation method and application thereof, relates to the technical field of biological targeting, and aims at solving the problem that a macrophage targeting nano-drug for inhibiting severe acute pancreatitis aiming at a TGM2 target is lacked in the prior art. The technical key points of the invention are as follows: the si-TGM2-loaded macrophage targeting nano material is provided, the si-TGM2-loaded macrophage targeting nano material is a lactoferrin modified cationic lipid nucleic acid drug, and the cationic lipid nucleic acid drug is prepared by coating si-TGM2 as shown in SEQ.ID. NO.1 with a cationic liposome. The si-TGM2-loaded macrophage targeting nanometer material disclosed by the invention has a wide application prospect in preparation of an acute pancreatitis diagnostic kit and a medicine.

The invention discloses an HSP70-targeting chimeric antigen receptor-macrophage and application thereof in treatment of noise-induced hearing loss, an extracellular domain of the HSP70-targeting chimeric antigen receptor comprises an HSP70 specific binding fragment, an intracellular domain comprises an IL-4 signal channel functional element, a signal switch type CAR structure of the HSP70 is formed, and the macrophage can be used for treating noise-induced hearing loss, so that the HSP70-targeting chimeric antigen receptor-macrophage can be used for treating noise-induced hearing loss. The HSP70-targeted chimeric antigen receptor-macrophage can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage, is used for mediating polarization of the macrophage to an M2 type and exerting an anti-inflammatory function, is proved to be capable of specifically responding to an inner ear inflammation microenvironment, switching an anti-inflammatory phenotype and protecting hair cells and auditory nerves, can be used for treating noise-induced hearing loss, and can be used for preparing the HSP70-targeted chimeric antigen receptor-macrophage. The limitation that traditional hearing-aid equipment supports treatment on symptoms is broken through, and the hearing-aid device has a remarkable application prospect.

The present invention relates to a CAR-macrophage targeting FAP and enhancing efferocytosis, as well as its preparation method and application. The CAR-macrophage contains a FAP-specific CAR targeting fibrosis and an efferocytosis enhancer Lgmn. The amino acid sequence of the FAP-specific CAR targeting fibrosis is shown in SEQ ID NO.1, and the nucleotide sequence is shown in SEQ ID NO.2; the amino acid sequence of the efferocytosis enhancer is shown in SEQ ID NO.3, and the nucleotide sequence is shown in SEQ ID NO.4. The CAR-macrophage can specifically target the FAP target and enhance the efferocytosis signaling pathway, thereby achieving a combination of CAR-macrophage therapy and enhancing intracellular degradation capacity. By expressing Lgmn protein, the rapid degradation and clearance of engulfed activated fibroblasts is enhanced, and the phagocytic effect of CAR-macrophages on activated fibroblasts is exerted and amplified, thereby achieving an efficient anti-fibrosis effect.

The invention discloses a metal organic framework material targeting bone marrow fat cells as well as a preparation method and application of the metal organic framework material, and belongs to the technical field of biomedical materials and tissue engineering. The material comprises: (1) a ZIF-8 core structure used for loading nucleic acid / small molecule drugs; (2) surface modification of lipid droplet targeting peptide: the lipid droplet targeting peptide is combined with a PEDF receptor to realize precise targeting; and (3) anti-miR-188 is loaded inside and is used for inhibiting adipogenic differentiation. The method at least has the following advantages: (1) a bone marrow adipocyte specific targeting MOF material is proposed for the first time, and bone metabolism intervention is converted from a mode of targeting osteoblast or macrophage to targeting adipocyte; (2) the MOF core can quickly respond to a marrow weak acid environment to realize accurate release; (3) the AdipoPep targeting peptide can obviously prolong the residence time of the bone marrow; and (4) adipogenic differentiation is significantly inhibited, osteogenesis microenvironment reconstruction is promoted, and an excellent bone mass recovery effect is shown in an osteoporosis model.

The present application relates to the technical field of biological medicine, and particularly relates to application of a nucleic acid vector encoding a macrophage monocarboxylate transporter MCT1 in preparation of a pharmaceutical composition for promoting corneal nerve regeneration and recovery of corneal sensitivity after corneal nerve injury. The present application finds that after corneal nerve injury, increasing the level of macrophage MCT1 can drive the change of the metabolic mode of macrophages to the direction of enhanced oxidative phosphorylation and reduced glycolysis, reduce the expression of local pro-inflammatory related factors, and increase the level of pro-regeneration factors and neurotrophic factors, thereby improving the regeneration of corneal nerve structure and the recovery of sensory function. Therefore, a macrophage-targeted or macrophage-biased expression vector containing a nucleic acid sequence encoding MCT1 can be used for preparation of a pharmaceutical composition for treating corneal nerve injury.

The present disclosure relates to compositions targeting tumor-associated macrophages. The compositions disclosed herein preferably comprise a glucan backbone, a tumor-associated macrophage targeting moiety, a targeting moiety linker, a payload, and optionally a payload linker. The present disclosure also provides methods of making such compositions. The present disclosure also provides methods of treatment using such compositions.

The invention relates to the technical field of biology, in particular to an in-vivo editing and metabolism reprogramming nano drug-loaded material for targeting macrophages as well as a preparation method and application of the in-vivo editing and metabolism reprogramming nano drug-loaded material. On the basis of a metal organic framework (MOF) material, CAR mRNA molecules targeting DLL3 are loaded in the MOF material, a macrophage-derived cell membrane is coated outside the MOF material, and the nano drug-loading material with the macrophage targeting capability is constructed. The material has the effects of specifically swallowing and killing tumor cells, improves the immunosuppression effect of a tumor microenvironment by utilizing the immune activation effects of succinic acid and manganese, and synergistically promotes the killing effect on small cell lung cancer. The macrophage in-vivo editing technology designed by the invention is a novel safe, efficient, simple and convenient tumor immunotherapy technology, overcomes the defect that CAR-T cannot enter the interior of a solid tumor, and solves the problem of tedious cell in-vitro amplification and gene editing procedures in the conventional CAR immunotherapy process; and a new strategy is provided for immunotherapy of small cell lung cancer with limited treatment means.

The invention discloses preparation and application of macrophage targeting nanoparticles entrapped with a cell burial function accelerant. The medicine for enhancing the intercellular function of the macrophages is a liver X receptor stimulant, and the liver X receptor stimulant comprises at least one of T0901317, GW3965, Ouabagenin and LXR-623. The surface of the targeting nanoparticle is coated with a macrophage cell membrane, and meanwhile, a urokinase type plasminogen activator receptor (uPAR) targeting ligand is modified. The nanoparticle can be efficiently accumulated at an inflammatory focus part by utilizing a macrophage cell membrane, and the modified targeting ligand is used for targeting the macrophage with damaged cell burial function, so that the cell burial function of the macrophage is enhanced, the polarization of the macrophage to an anti-inflammatory phenotype is promoted, the release of anti-inflammatory and proinflammatory cytokines is regulated, and the anti-inflammatory effect of the nanoparticle is improved. And finally, the inflammatory microenvironment of a focus part is regulated and controlled, so that a good effect of treating autoimmune diseases is achieved.

The invention relates to the technical field of biological medicine, in particular to an efficient macrophage targeting vesicle system as well as a preparation method and application thereof. The vesicle system is a chimeric vesicle (mHEs), and is prepared from extracellular vesicles (M2-EVs) derived from M2 type macrophages and apoptotic small bodies (MSC-ABs) derived from bone marrow mesenchymal stem cells. The vesicle system provided by the invention can realize specific recognition and functional regulation of macrophages, thereby playing an efficient therapeutic role in pathological processes such as tissue inflammation repair, myocardial infarction, ischemia-reperfusion injury and immune metabolism remodeling.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a Tim-4 functional structural domain-based macrophage targeted nanomaterial combined intestinal selective biological preparation in inflammatory bowel diseases. Specifically, according to the macrophage targeting nano material based on the Tim-4 functional structural domain, through precise delivery of anti-inflammatory molecules and combination with a clinical drug (vializumab), dual regulation and control of innate immunity and adaptive immunity are achieved, so that the inflammatory bowel disease is efficiently treated, and therefore the macrophage targeting nano material has good practical application value.

The present invention belongs to the field of nanobiotechnology and discloses a plant-derived apoptosis-mimicking extracellular vesicle, a preparation method thereof, and an application thereof. The preparation method comprises the following steps: extracting plant-derived extracellular vesicles from plant tissues, and fusing the plant-derived extracellular vesicles with a solution containing apoptosis signal phosphatidylserine (PS) to obtain the plant-derived apoptosis-mimicking extracellular vesicles. The plant-derived apoptosis-mimicking extracellular vesicles of the present invention are derived from natural plants and have good biocompatibility compared to apoptotic cell vesicles derived from mammalian cells, and are less likely to cause immune rejection reactions in the body; after modification with phosphatidylserine (PS), compared with natural plant-derived extracellular vesicles, the plant-derived apoptosis-mimicking extracellular vesicles of the present invention have significantly improved macrophage targeting, inhibition of macrophage inflammatory response, and improvement of RA.

The invention discloses application of PLGA (poly (lactic-co-glycolic acid)) to treatment of lean non-alcoholic fatty liver disease by taking Marco + macrophages as targets, and belongs to the technical field of biological medicines. The invention proves that the tail vein injection PLGA specifically targets abnormally increased Marco + macrophages in the liver of lean non-alcoholic fatty liver, effectively inhibits the inflammatory response and fibrosis process mediated by the Marco + macrophages, remarkably reduces liver lipid deposition, relieves insulin resistance and recovers the fat storage function of adipose tissue. The invention provides a new strategy for treating the lean non-alcoholic fatty liver disease by targeting the PLGA to the Marco + macrophages for the first time, expands the clinical transformation potential of the PLGA in the treatment of the metabolic liver disease, and provides a new scheme for the intervention and treatment of the lean non-alcoholic fatty liver disease.

The invention discloses a ZP3-targeting chimeric antigen receptor macrophage and application thereof, and relates to the technical field of biological medicine, the macrophage expresses a chimeric antigen receptor, and the chimeric antigen receptor comprises a signal peptide, an anti-ZP3 single-chain antibody, a hinge region, a transmembrane domain and an intracellular signal region; the anti-ZP3 single-chain antibody comprises an antibody light chain variable region, a GS linker and an antibody heavy chain variable region, the amino acid sequence of the antibody light chain variable region is as shown in SEQ ID NO: 1, and the amino acid variable region sequence of the antibody heavy chain variable region is as shown in SEQ ID NO: 2. The chimeric antigen receptor macrophage constructed based on the chimeric antigen receptor shows remarkable anti-tumor activity in vitro and in vivo, including enhanced tumor cell phagocytic ability and killing efficiency, solves the problems of insufficient target specificity, difficult cell infiltration and tumor microenvironment inhibition in liver cancer immunotherapy, and has a broad application prospect. And a treatment strategy with high targeting property, strong wettability and good safety is provided for patients with hepatocellular carcinoma.

This invention belongs to the field of biomedical technology and provides the application of exosome-derived TRIM59 inhibitors in regulating macrophage M2 polarization and combating oral squamous cell carcinoma. The TRIM59 inhibitor uses exosomes derived from oral squamous cell carcinoma tissue as carriers, with the surface modified with the M2 macrophage-targeting molecule M2pep, internally loaded with TRIM59 inhibitors and KRT6B inhibitors, and loaded with STING pathway agonists. This invention relies on the microenvironment targeting and membrane surface targeting modification of tumor-derived exosomes to precisely deliver TRIM59 inhibitors and KRT6B inhibitors to M2 macrophages and tumor cells. By silencing TRIM59, the resistance of M2 macrophages to the STING pathway is relieved, forming a temporal synergistic effect of first unlocking and then activating with the STING agonist, driving macrophages to M1 polarization.

The invention discloses a CX3CL1 targeting chimeric antigen receptor-macrophage and application thereof in treatment of GJB2 mutation related hereditary deafness, the CX3CL1 targeting chimeric antigen receptor-macrophage directly converts a CX3CL1 mediated pro-inflammatory signal into an anti-inflammatory signal, so that the macrophage is directionally polarized to an M2 type, the anti-inflammatory repair function is exerted, and the GJB2 mutation related hereditary deafness can be treated by the CX3CL1 targeting chimeric antigen receptor-macrophage. A cochlea injury microenvironment is specifically responded, anti-inflammatory repair phenotypes are switched, and cochlea epithelial cells and spiral ganglion neurons are protected; the GJB2 mutation-related hereditary deafness inner ear local inflammation can be accurately improved, apoptotic cell debris removal is promoted, the whole body immune homeostasis is not interfered, and the GJB2 mutation-related hereditary deafness inner ear local inflammation has a remarkable drug treatment application prospect.

The present disclosure relates to compositions that target tumor-associated macrophages. The compositions disclosed herein preferably comprise a glucan backbone, a tumor-associated macrophage targeting moiety, a targeting moiety linker, a payload, and optionally a payload linker. The present disclosure also provides methods for making such compositions. The present disclosure also provides treatment methods using such compositions.

The invention discloses an application of a macrophage subgroup in improving the treatment effect of AK112 (Adenosine Kinase 112). The macrophage subgroup is APOE + KRT18-CCL20-macrophages. It is found for the first time that a specific macrophage subset in a tumor microenvironment (TME) can significantly improve the AK112 double-antibody tumor killing activity, and a new target is provided for overcoming clinical drug resistance. Meanwhile, a matched flow cytometry kit is developed, the kit comprises 12 antibody combinations, and the subgroup marker is synchronously and accurately detected by a single tube through a full-spectrum flow technology. The sensitivity and the specificity are high, the AK112 treatment response can be dynamically monitored, and the disease progress can be predicted. According to the macrophage targeted synergistic mechanism and the integrated detection system, a combined treatment strategy is provided for AK112 drug-resistant patients, and a pioneering tool is provided for individualized curative effect evaluation.

The present disclosure provides methods and compositions related to the combination therapy of a macrophage-directed immunotherapy and a cytokine (e.g., IL-10). The combination of the macrophage-directed immunotherapy and a cytokine is useful in treating and / or preventing cancer (e.g., lung cancer) in a subject. Therapies that activate macrophages are emerging in cancer immunotherapy. One potential therapeutic target is the CD47-SIRPa, interaction, which acts as a myeloid immune checkpoint. Cluster of Differentiation 47 (CD47) is highly expressed on many different types of cancer cells, including lung cancer cells. CD47 binds to an inhibitory receptor, signal regulatory protein alpha (SIRPa,), that is expressed on the surface of macrophages and other myeloid immune cells.