62results about How to "Enhance anti-tumor immune response" patented technology

Methods and devices for isolating and diagnosing disease with a cell adhesion matrix system, mimicking a metastatic, cardiovascular or placental environment, are disclosed. The cell adhesion matrix facilitates the enrichment of target cells such as metastatic tumor cells, fetal cells and endothelial progenitor cells from a fluid sample such as blood for diagnostic and therapeutic applications in treating patients afflicted with disease, such as cancerous, cardiovascular and fetal diseases, as well as for research applications in molecular analysis of metastatic, and cardiovascular and fetal diseases. Blood test prototypes and methods for the cell enrichment and detection of circulating tumor and endothelial cells using multiplex molecular analysis are described herein. In addition, methods and compositions for determining host immunity to tumor in subjects with risk of cancer progression and methods for isolating an enriched fraction of fetal cells from pregnant females for prenatal diagnosis are also described herein.

The invention relates to a novel EGFR and CD47 targeting bispecific antibody fusion protein, and a preparation method and application thereof. The novel bispecific antibody fusion protein Bi-SP provided by the invention has a function of simultaneously binding EGFR and CD47; and at the same time of binding the EGFR, the bispecific antibody fusion protein can block or prevent the binding of the CD47 and SIRPalpha, reactivate the phagocytosis of macrophages and enhance an antitumor immune response, thereby achieving a better antitumor effect.

The invention relates to a preparation method and application of an anti-tumor vaccine based on cell microvesicles and aims to effectively solve problems in preparation of anti-tumor vaccines high inyield, good in universality, strong in killing effect on tumor cells and capable of controlling tumors by improving tumor microenvironments, repairing an immune system and enhancing anti-tumor immuneresponse of organisms. The preparation method comprises the following steps: preparing tumor cell microvesicles loaded with immunomodulators and connecting the surfaces of the microvesicles with adjuvant-loaded liposome to stably form the anti-tumor vaccine. The prepared anti-tumor vaccine is high in yield, good in universality, strong in killing effect on tumor cells and capable of improving tumor microenvironments, repairing an immune system and enhancing anti-tumor immune response of organisms; the method is simple in process and high in efficiency; and the prepared microvesicles are derived from cells, are sufficient in quantity and wide in source, are easy for large-scale production, improve the bioavailability of adjuvants, are effectively applicable to preparation of anti-tumor vaccines based on the cell microvesicles, and can be applied to prevention and treatment of different types of tumors.

The invention relates to methods for diagnosing cancer and determining the responsiveness to chemotherapyin a subject based on the detection of HSP70-expressing exosomes in a bodily fluid sample obtained from said subject. The invention also relates to methods for treating cancer and in particular methods for restoring or enhancing the anti-tumor immune response in a patient in need thereof by inhibiting the activation MDSC as well as methods for inhibiting or reducing HSP70-expressing exosomes-mediated tumor resistance against a chemotherapeutic agent and therefore methods for restoring or enhancing the efficacy of said chemotherapeutic agent.

The invention provides an organic AIE photosensitive probe with mitochondrial targeting and a preparation method and application thereof, and belongs to the technical field of antitumor drugs. The organic AIE photosensitive probe with mitochondrial targeting has a structure as shown in the following formula I in the specification. According to the organic AIE photosensitive probe, mitochondrial ROS oxidative stress is triggered, a large amount of calreticulin translocation is induced to be generated, the immunogenicity of tumor cells is effectively improved, and lasting anti-tumor immune response of an organism is triggered. Therefore, the organic AIE photosensitive probe is applied to preparation of drugs for tumor cell immune response or preparation of reagents for triggering the mitochondrial ROS oxidative stress and inducing generation of calreticulin transposition.

The invention discloses the field of tumor cellular immunotherapy and particularly relates to a tumor cell vaccine which is modified by a PD-1 neutralizing antibody with combination of a GM-CSF factor and a preparation method thereof. In the invention, tumor cellular vaccine therapy is creatively combined with antibody therapy which relieves tumor immune-suppression, so that the prepared tumor cell vaccine simultaneously secreting the PD-1 neutralizing antibody and the GM-CSF factor can not only relieve the immune-suppression status of a tumor micro-environment but also enhance an antitumor immune reaction. The tumor cell vaccine is good in antitumor treatment effect, is excellent in development value and provides a new approach of tumor cellular immunotherapy.

We have recently identified (a) ectocalreticulin as the main source of immunogenicity of cancer cell death induced by chemotherapy or radiotherapy, (b) ectoERP57 as critical protein for inducing cell surface exposure of calreticulin, and (c) that ectoERP57 and ectocalreticulin are cotranslocated together to the tumor cell surface by the mediator of the inhibition of PP1 / GADD34 complex. Here, I show the design of a peptide that inhibits the interaction between PP1 and GADD34 complex. These inhibitor peptide (a) induce ectocalreticulin and ectoERP57 in a variety of tumor cell lines by the mediator of the inhibition of the interaction between PP1 and GADD34, (b) increase the phagocytosis of anticancer targeted proapoptotic peptide and chemotherapy-treated tumor cells by dendritic cells, and (c) improve highly the anticancer activity of proapoptotic peptides and chemotherapy by suppressing or reducing the tumor growth in several isogenic mouse models of colon, mammary, and fibrosarcoma tumors and by increasing the lifespan of transgenic adenocarcinoma mouse prostate mice. These results suggest that these targeted peptides combination approach could serve as a new powerful autonomous anticancer therapy.

The invention discloses an application of gamma interferon induced lysosomal sulfydryl reductase GILT in enhancement of anti-tumor immune response. It is found that high expression of GILT can promote infiltration of T cells in breast cancer tissue. GILT is overexpressed in breast cancer cells, and the killing ability of T cells to the breast cancer cells can be enhanced. The GILT provided by the invention can effectively promote T cell mediated anti-tumor immune response, and the breast cancer immunotherapy effect can be improved by activating GILT expression.

The invention discloses an anti-tumor immunotherapy nano-drug delivery system. The anti-tumor immunotherapy nano-drug delivery system consists of a taxol / anionic cyclodextrin-DNA / mannose modified trimethyl chitosan nano-composite; the anti-tumor immunotherapy nano-drug delivery system is composed of taxol, anionic cyclodextrin, DNA and mannose modified trimethyl chitosan; and the anti-tumor immunotherapy nano-drug delivery system is targeted to dendritic cells by virtue of a mannose ligand. The invention also discloses a construction method of the anti-tumor immunotherapy nano-drug delivery system. The comprehensive immune drug delivery system provided by the invention not only can enhance the antitumor immunity response of a tumor bearing body but also can inhibit or reverse tumor immune escape; and the nano-drug delivery system is simple and convenient in preparation method and high in targeting efficiency.

[Problem to be Solved]It is an object of the present invention to provide a composition, which induces immunity to tumor cells and is also able to induce inhibition of tumor growth.[Solution]Provided is a composition for inducing tumor immunity, comprising ALAs.

The invention discloses a bidirectional regulating therapeutic vaccine for gliomas and a preparation method thereof. The vaccine is a compound of FAT10 multivalent epitope peptide and a Tim-3 genetic recombinant expression vector, wherein the FAT10 multivalent epitope peptide is composed of epitope FAT10154-162 / FAT10155-163 / FAT1049-57 and a trans-membrane sequence HIV-Tat40-48, an endoplasmic reticulum retention signal sequence DELK and a joint sequence; the trans-membrane sequence is located at an amino terminal; the endoplasmic reticulum retention signal sequence is at a carboxyl terminal; the epitope is connected to the trans-membrane sequence or the endoplasmic reticulum retention signal sequence through the joint sequence. The vaccine can successfully enter cells and target endoplasmic reticulum, and effectively promote the epitope FAT10154-162 / FAT10155-163 / FAT1049-57 to enter an MHC-1 (major histocompability complex-1) antigen presentation pathway to excite specific CTL (cytotoxic T lymphocyte) response; meanwhile, the Tim-3 plays roles in inhibiting immune escape and assisting to simulate T cell activation, so as to generate a wide immune activation effect and to induce strong antitumor immunity.

The present invention relates to methods for enhancing the potency of the immune checkpoint inhibitors. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen, the method comprising administering a pharmaceutically effective amount of a SK1 inhibitor to a subject in combination with the immune checkpoint inhibitor.

The invention discloses a chimeric antigen receptor T lymphocyte and an application thereof to preparation of a product for treating solid tumors. A chimeric antigen receptor in the chimeric antigen receptor T lymphocyte sequentially comprises a human CD8 lead peptide, an anti-Siglec-15 single-chain antibody, a human CD8 hinge transmembrane region, a human 4-1BB intracellular region, a human CD3 zeta intracellular region, a self-cleavage peptide, a CSF2Ra signal peptide, an EGFRt protein, a self-cleavage peptide and a human CD27. Experiments prove that the chimeric antigen receptor T lymphocyte provided by the invention highly expresses IFN gamma and CD107a, has a strong killing function on Siglec-15 positive tumor cells, and has killing efficiency of more than 80% under the condition thatthe effect-target ratio is 1: 1. A tumor transplantation model experiment shows that the chimeric antigen receptor T lymphocyte also has a strong killing function on Siglec-15 positive tumor cells inan animal body.

The invention relates to an oncolytic virus vaccine and adoptive immune cell combination therapy. Specifically, the present disclosure relates to a modified matrix protein (M) of recombinant oncolyticrod-like virus, an oncolytic virus, an oncolytic virus vaccine, and combination therapy of the oncolytic virus vaccine with endogenous and adoptive immune cells. The present disclosure also providesantineoplastic preparations, including independent administration for oncolytic virus, oncolytic virus vaccine, and multiple-route and combination administration therapies. The present disclosure alsoprovides methods and strategies of the combination therapy for treating cancers, as well as a method for preparing an oncolytic virus vaccine and a tumor antigen specific central memory CD8+T cell population. According to the combination therapy provided by the invention, all potentials of adoptive immune cells and endogenous T cells aiming at various tumor-associated antigens can be developed, so that primary and secondary metastatic primary tumors are effectively eliminated, immune escape is prevented, long-time memory protection is generated, and the effect of radically treating tumors isachieved.

The invention relates to the technical field of biomedicine, in particular to an EGFP-Wnt2 fusion protein antigen, a Wnt2 monoclonal antibody and an application of a Wnt2 monoclonal antibody. The EGFP-Wnt2 fusion protein antigen is mainly a fusion protein of EGFP and a full-length amino acid sequence of a humanized Wnt2 signal-erasing peptide. The EGFP-Wnt2 fusion protein antigen comprises an EGFPamino acid sequence, a TEV restriction enzyme cutting site and a FLAG tag sequence, and the Wnt2 signal-erasing peptide full-length amino acid sequence, a 6* His tag sequence and an anti-Wnt2 monoclonal antibody can be used for inhibiting immune escape and growth of tumor cells. When the Wnt2 monoclonal antibody disclosed by the invention is combined with the human Wnt2 antigen secreted by cells,the promotion of the cell on the formation of an inhibitory immune microenvironment in a tumor is antagonized, and the immune escape and growth of the tumor cell are inhibited. The Wnt2 monoclonal antibody provided by the invention can be used in immune treatment of solid tumors such as esophageal squamous carcinoma, gastric cancer, pancreatic cancer, colorectal colon cancer, lung cancer, breastcancer, glioma, liver cancer and the like.

The invention relates to the field of biotechnologies, and discloses an antitumor composition, a co-expression vector for the same and application of the antitumor composition. The antitumor composition, the co-expression vector and the application have the advantages that combination of 1L-36 gamma and PD-1 (programmed death-1) / PD-L1 (programmed death-ligand 1) signal blocking agents on tumor sites is demonstrated, antitumor immune response in tumor micro-environments can be effectively promoted, and tumor growth can be obviously inhibited; the lifetime of tumor-bearing mice can be greatly prolonged, novel and effective tumor immunotherapy is created, and theoretical and method foundations can be laid for further developing corresponding tumor immunological preparations.

The invention relates to an immune cell modified by a suppressor protein blocking type chimeric antigen receptor and application of the immune cell. The immune cell modified by the suppressor protein blocking type chimeric antigen receptor is used for a medicine for treating malignant tumors, and the suppressor protein and the chimeric antigen receptor are co-expressed in the immune cell; the nucleotide sequence of the suppressor protein is as shown in SEQ ID NO: 3, and the protein sequence is as shown in SEQ ID NO: 4; and the nucleotide sequence for blocking co-expression of the suppressor protein and the chimeric antigen receptor is as shown in SEQ ID NO: 5, and the protein sequence is as shown in SEQ ID NO: 6. From the perspective of blocking transduction of a negative regulation signal of the immune cell, the CAR-T cell expresses the suppressor protein, the transmission of the negative regulation signal is weakened / blocked, and the anti-tumor activity of the CAR-T cell is enhanced; and the anti-tumor immune response can be enhanced without being combined with an immune checkpoint antibody drug, the drug cost is reduced, the dosage can be accurately determined, and the curative effect is exact and remarkable.

The present invention relates to the combined use of a neuropilin-1 (Nrp-1) neutralizing agent and of a programmed cell death-1 (PD-1) neutralizing agent for killing cancer cells, typically for treating cancer, as well as to corresponding pharmaceutical compositions and kits, and to corresponding diagnostic and therapeutic methods. The invention further relates to in vitro, ex vivo and in vivo methods for detecting CD8+ TILs capable of recognizing cancer cells, for predicting the response of a subject to anti-PD-1 treatment of cancer, and for identifying a subject who responds therapeutically to a treatment of cancer with an antibody combination therapy comprising anti-Nrp-1 and anti-PD-1 antibodies.

The present invention provides, in some embodiments, methods of promoting an immune response in a subject in need thereof, comprising administering to a subject a population of immune cells that express an exogenous enzyme that facilitates immune cell function in a nutrient-poor environment. Other embodiments of the invention include methods of promoting an immune response to a tumor in a subject in need thereof, comprising administering to the subject an effective amount of an agent that provides a one-carbon unit (e.g., formate) and an agent that promotes an anti-tumor response, and methods of promoting an immune response to a tumor in a subject in need thereof, comprising administering to a subject an effective amount of an agent that inhibits consumption of metabolic fuels by tumor cells. The invention also provides, in other embodiments, compositions comprising an ex vivo population of immune cells expressing an exogenous enzyme that enhances immune cell function in nutrient poor environments, and compositions comprising a nucleic acid expression construct encoding an inhibitor of glucose metabolism, and a pharmaceutically acceptable carrier or excipient.

The present invention relates to methods for enhancing the potency of the immune checkpoint inhibitors. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen, the method comprising administering a pharmaceutically effective amount of a SK1 inhibitor to a subject in combination with the immune checkpoint inhibitor.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a glycosyl modified naphthalimide-polyamine conjugate as well as a preparation method and application thereof. According to the invention, a naphthalimide mother nucleus is modified by glycosyl groups such as peracetyl or deprotected glucose, galactose, mannose, rhamnose, maltose, lactose, cane sugar and the like, so that the glycosyl transporter (GLUTs) with high expression of targeted tumor cells is realized, and better targeting on liver cancer and advanced liver cancer is realized. The novel naphthalimide-polyamine conjugate targeting liver cancer and advanced liver cancer is found for the first time, the naphthalimide complex capable of regulating subcellular organelles is found for the first time, and a new thought and a research direction are provided for treatment of the advanced liver cancer.

The invention provides an application of blocking tumor-derived ILT4 in adoptive T cell therapy. Researches find that the tumor-derived ILT4 has an induction effect on microenvironment T cell aging, molecular and metabolic mechanisms of the tumor-derived ILT4 are explored in detail, and it is proved from a preclinical model that the targeted ILT4 can reverse the immunosuppressive microenvironmentof tumors and participate in targeted therapy of malignant tumors, and a B6 mouse malignant melanoma adoptive T cell immunotherapy model is further constructed, and the feasibility of ILT4 blocking combined ACT therapy is studied. An effective means is provided for overcoming ACT treatment drug resistance.

The invention discloses application of combined medication of bacteroides fragilis zwitterionic capsular polysaccharide and an immune checkpoint inhibitor in prevention and treatment of tumors of a genitourinary system. A large number of experiments prove that when the capsular polysaccharide A of the bacteroides fragilis, especially the bacteroides fragilis ZY-312 with the preservation number of CGMCC No.10685, and an immune checkpoint inhibitor are combined for medication, the anti-tumor immune response of a body can be enhanced by regulating and controlling the levels of T cells and anti-tumor immune factors, and then the aim of preventing and treating the tumors of the genitourinary system is achieved.

The invention discloses a polymer vesicle nano STING agonist as well as a preparation method and application thereof. The method includes: adding the STING agonist solution into the buffer solution, adding the polymer solution, performing stirring, and performing dialyzing to obtain the polymer vesicle nano STING agonist. The polymer vesicle nano STING agonist disclosed by the invention is formed by loading an STING agonist on polymer vesicles; the polymer vesicles are small in particle size, can efficiently load the STING agonist and have high biological safety, drug loading stability and reduction responsiveness, the vesicles are used for loading the STING agonist for the first time and combined with radiation to be used for treating malignant melanoma, uptake of antigen presenting cells (APC) to the STING agonist is improved through the nano-scale characteristic of the polymer vesicles, the retention of the STING agonist in a tumor part is prolonged, the immunocompetence of the STING agonist is greatly improved, and the activation of an STING pathway is enhanced.

The invention discloses application of drug combination of bacteroides fragilis and a PD-1 antibody and / or a PD-L1 antibody in prevention and treatment of tumors of a genitourinary system. A large number of experiments prove that the bacteroides fragilis, especially the bacteroides fragilis ZY-312 with the preservation number of CGMCC No.10685, can be used for effectively preventing and treating the tumors of the genitourinary system by regulating immune factors, improving the state of immune cells and enhancing the anti-tumor immune response of a body.

The invention features a composition comprising an immuno-stimulatory compound and a pHLIP® peptide, e.g., an immunostimulatory compound that comprises a cyclic purine dinucleotide, which binds to a stimulator of interferon genes (STING) such as a cGAMP cyclic compound inside a cell.

The invention relates to a preparation method of a near-infrared response nanocage and application of the near-infrared response nanocage in tumor immune combined therapy. The preparation method of the near-infrared response nanocage comprises the four steps of preparing AuNC, preparing AuNC-coated mSiO2, preparing ASP and preparing an ASP intersection V. The near-infrared response nanocage has the advantages of good biocompatibility, safety, near-infrared region photothermal conversion, high drug loading capacity and the like. The drug-loaded nanocage can effectively deliver drugs into tumor cells and convert light energy into heat energy, light heat and a BRAF inhibitor are combined to inhibit tumor growth, induce immunogenic necrosis of the tumor cells, promote release of tumor-related antigens and generate systematic anti-tumor immune response, and the drug-loaded nanocage cooperates with an anti-PD-1 antibody to inhibit tumor growth. According to the gold nanocage, MAPK molecular targeting and anti-PD-1 immune combined treatment is realized, and a new strategy is provided for tumor treatment.

The invention discloses application of bacteroides fragilis and / or zwitterionic capsular polysaccharide thereof in preparation of drugs for preventing and treating digestive system tumors. A large number of experiments prove that the bacteroides fragilis ZY-312 with the preservation number of CGMCC No.10685 and the zwitterionic capsular polysaccharide thereof can relieve inflammatory response, protect normal tissues, improve anti-tumor immune response of organisms and effectively prevent and treat digestive system tumors.

The invention discloses a cancer combined treatment composition. The effective components comprise CAR-T cells and an epigenetic regulator, the CAR-T cells can recognize at least one cancer specific antigen or cancer related antigen; and the epigenetic regulator comprises at least one of a CDK7 inhibitor and a BRD4 inhibitor. Compared with a treatment mode of combining CAR-T with an inhibitor or an antibody for blocking a single immune escape pathway, the treatment mode of combining the CAR-T and the epigenetic regulator has a wider inhibition effect on a tumor microenvironment and is easier to operate and implement compared with other schemes for blocking multiple immune escape pathways in CAR-T treatment.