35 results about "Antineoplastic Immunotherapeutic" patented technology

The invention belongs to the technical field of biological medicines, and particularly relates to application of bleomycin or bleomycin analogues in preparation of an immunopotentiator. The invention also provides a pharmaceutical composition and application of the pharmaceutical composition in preparation of drugs for treating and / or preventing cancers. The pharmaceutical composition comprises bleomycin, bleomycin analogues or a combination thereof and an anti-tumor immunotherapeutic agent.

The invention relates to the field of biomedicine, in particular to a gene for reversing CD8 + T cell depletion to enhance an immunotherapy effect and application of the gene. The invention firstly provides a medicine for reversing or improving the depletion state of CD8 + T cells. The medicine comprises an inhibitor for inactivating or inhibiting UBASH3A gene expression in the CD8 + T cells and / or an inhibitor for reducing the activity of a signal inhibition factor 2. The invention further provides a composition for enhancing the curative effect of anti-PD-1 / PD-L1 immunotherapy, a kit for predicting the effect of anti-T-cell anti-tumor immunotherapy and the like. The invention provides a new tumor immunotherapy target based on the STS2 protein and an application scheme thereof by deeply researching the action mechanism of the STS2 protein in anti-tumor immunotherapy, brings new breakthrough and progress to the field of tumor immunotherapy, and has important scientific significance and clinical application value.

The preparation method comprises the following steps: preparing FA-PEG-TK-PBLA-OCT and TPEN (at) NT, then carrying out a reaction on the FA-PEG-TK-PBLA-OCT and the TPEN (at) NT, and inducing TPEN (at) NT encapsulation and micelle formation, so as to prepare STCNs. The STCNs have dual functions of enabling cells to generate endogenous copper death and enhancing antitumor immunotherapy benefits, have good effects on various solid tumor cell strains and PDX animal models, and have relatively high clinical application values.

The invention discloses a temperature-sensitive gel preparation containing a glutaminase inhibitor as well as a preparation method and application of the temperature-sensitive gel preparation, and belongs to the technical field of biological medicines. The temperature-sensitive gel preparation comprises outer-layer gel and inner-layer gel, the inner-layer gel is coated with the outer-layer gel, the outer-layer gel accounts for 40-75% of the total mass of the temperature-sensitive gel preparation, and the inner-layer gel accounts for 25-60% of the total mass of the temperature-sensitive gel preparation; the outer-layer gel is prepared from the following raw materials: an outer-layer gel matrix, a glutaminase inhibitor, a photosensitizer and a stabilizer; the raw materials of the inner-layer gel comprise an inner-layer gel matrix and an immune checkpoint inhibitor. According to the temperature-sensitive gel preparation, through photo-thermal control, the glutaminase inhibitor is firstly released to relieve the immunosuppression state, then the immune checkpoint inhibitor is released to kill tumors, and the glutaminase inhibitor and the immune checkpoint inhibitor act synergistically, so that efficient anti-tumor immunotherapy is achieved.

The invention belongs to the field of PD-L1 / PD-1 monoclonal antibody tumor immunotherapy, and aims to provide a new research and development direction of PD-L1 / PD-1 monoclonal antibody tumor immunodetection or immunotherapy adjuvant drugs and a new drug combination mode. Experimental results of the invention verify that the invention discloses an application of a reagent for detecting the expression quantity of USP51 in preparation of a detection kit for preparing a PD-L1 / PD-1 monoclonal antibody tumor immunotherapy drug, and discloses an application of a combination of a USP51 inhibitor and a PD-L1 / PD-1 monoclonal antibody drug in preparation of a drug for treating melanoma. The invention discloses an application of a combination of a CD200 inhibitor and a PD-L1 / PD-1 monoclonal antibody in preparation of a drug for treating melanoma, and further discloses an application of a combination of liposome-coated bleomycin and a PD-L1 / PD-1 monoclonal antibody in preparation of a drug for treating melanoma, so that the adverse reaction of bleomycin can be reduced.

The application relates to the technical field of tumor drugs, in particular to application of METTL5 as a tumor immunotherapy targeting site. The base sequence of the METTL5 is shown in SEQ ID No. 1; wherein the METTL5 is a brand-new RNAm6A methyltransferase, is closely related to ribosome translation function, and can regulate the translation of a tumor immune key regulator IL-27; therefore, the METTL5 is used as the tumor immunotherapy targeting site, the expression of the METTL5 related genes or coding proteins is inhibited through targeting, the body anti-tumor immunity can be effectively stimulated, the METTL5 becomes the targeting site capable of enhancing the response rate of tumor immunotherapy, and the METTL5 used as the tumor treatment target point has a wide application prospect in the anti-tumor immunotherapy.

The invention belongs to the technical field of biological medicines, and particularly relates to application of an antiviral drug acyclovir in preparation of a tumor immunotherapy drug. According to the invention, acyclovir is utilized to induce macrophages to become an M1 phenotype, the phagocytic function and the antigen presentation capability of the macrophages are enhanced, and the maturation of dendritic cells is promoted, so that the anti-tumor effect is realized. In an effective concentration which is non-toxic to a macrophage line RAW264.7, acyclovir significantly promotes phenotype transformation of macrophages to M1, and significantly enhances the cell phagocytic ability and antigen presentation ability of the macrophages. Meanwhile, the acyclovir in an effective concentration can also remarkably promote maturation of bone marrow-derived dendritic cells, so that new application of the acyclovir in the field of tumor immunotherapy is found. According to the method, the application range of acyclovir and immune cell immunotherapy is expanded, and a new feasible clinical treatment scheme is provided for anti-tumor immunotherapy.

The invention relates to a bionic intelligent microneedle tumor vaccine as well as a preparation method and application thereof. According to the vaccine, coaxial electrostatic spraying is utilized to construct a drug-loaded microsphere with a core-shell structure, the drug-loaded microsphere is coated with cancer cell-derived membrane protein, and then the drug-loaded microsphere is fixed at the needle point part of a soluble microneedle in a centrifugal manner, so that local drug delivery of crossing a cuticle layer and accurately delivering the drug-loaded microsphere to a corium layer is realized. The microsphere can load demethylated drugs DAC and TAM at the same time, and realizes responsive controlled release in a tumor microenvironment. A plurality of tumor-associated antigens and apoptosis-associated injury-associated molecular patterns carried by the cancer cell membrane protein can promote the maturation of dendritic cells and activate the specific T cell mediated anti-tumor immune response. In conclusion, the microneedle vaccine system integrates multiple functions of precise delivery, controllable release, chemical kinetics treatment, epigenetic regulation, immune activation and the like, the anti-tumor immunotherapy effect can be effectively enhanced, and a new strategy is provided for tumor immunotherapy.

The invention belongs to the technical field of protein polypeptides, and particularly discloses a CD93 affinity peptide and application thereof in preparation of antitumor drugs or detection reagents. The polypeptide with a CD93 protein affinity effect is obtained through repeated screening and optimization, and an affinity blocking activity experiment proves that the CD93 affinity peptide can affine an extracellular IgV-like structural domain of the CD93 protein and block the interaction of CD93 / IGFBP7 protein. An HUVECs cell in-vitro migration experiment and a tube formation experiment verify that the CD93 affinity peptide can inhibit migration of HUVECs cells and tube formation, promote normalization of tumor vascular functions and further inhibit growth of tumors, and has no obvious toxic or side effect. The CD93 affinity peptide provided by the invention can be used for preparing anti-tumor drugs (including anti-tumor immunotherapy drugs) or detection reagents taking CD93 as a target spot, has a better medical application prospect, and provides a new choice for tumor immunotherapy.

The invention belongs to the field of biological medicine, and particularly relates to novel application of a functional regulator of xylosyltransferase 1 (XYLT1) in preparation of drugs for resisting human immunodeficiency virus (HIV) infection and / or resisting tumor immunotherapy. In-vitro experiments prove that up-regulation of expression or activity of XYLT1 can inhibit HIV virus replication (such as reduction of p24 antigen and virus infectivity) and enhance the curative effect of a broad-spectrum neutralizing antibody (such as 3BNC117); meanwhile, the XYLT1 can mediate the degradation of PD-L1 protein, relieve the inhibition on T cells and enhance the anti-tumor killing activity of CD8T cells. The invention provides a new target spot and a combined treatment strategy for immunotherapy of viral diseases and tumors.

This invention discloses an immune cell with enhanced anti-tumor effect, its preparation method, and its application. Experiments using this invention show that... SERTAD1 CD8 gene overexpression + T cells can enhance their function in anti-tumor immunotherapy. SERTAD1 Gene overexpression can downregulate CD8 + The expression of immune checkpoint molecules on T cells upregulates the expression of mRNAs of tumor-killing cytokines. In the MC38-OVA subcutaneous tumor model, Naïve CD8 cells were extracted from OT-I mice. + T cells were infected with a virus to overexpress SERTAD1, followed by adoptive transfer to mice. The results showed that SERTAD1 overexpression enhanced CD8 expression. + T cells kill MC38-OVA cells, inhibit the growth of MC38-OVA tumor cells, and overexpress SERTAD1 CD8. + The tumor volume and weight in the T-cell adoptive group were significantly smaller than those in the control group.

The invention discloses a chiral iridium complex nano assembly as well as a preparation method and application thereof. The chiral iridium complex nano assembly disclosed by the invention is obtained by carrying out ultrasonic treatment, dialysis and filtration on delta-IrBMS8-mPEG or lambda-IrBMS8-mPEG. The chiral iridium complex nano assembly disclosed by the invention can induce chirality-dependent ferroptosis in a photodynamic therapy (PDT) process and cooperate with blocking of immune checkpoints, so that an anti-tumor immune process is effectively activated, and an efficient synergistic treatment effect is achieved. The preparation method disclosed by the invention is simple and controllable in process, excellent in biological safety and suitable for anti-tumor immunotherapy.

The invention provides a switch element capable of realizing specific response and a lysosomal targeting chimera containing the response switch, which are verified to be capable of specifically degrading target protein contained in tumor cells only in a tumor microenvironment without influencing functions of normal cells of an organism, are simple and convenient in preparation steps, can be used for preparing immune checkpoint blocking drugs, and can be used for preparing immune checkpoint blocking drugs. The tumor treatment effect is improved, the transformation problem and the problem of tumor toxicity in target removal in the prior art are solved, and efficient and safe anti-tumor immunotherapy can be achieved.

The invention discloses an application of a fusobacterium specific antibacterial peptide in preparation of a medicine for improving the anti-tumor immunotherapy effect of a PD-1 antibody. It is found that the fusobacterium specific antibacterial peptide combined with the PD-1 antibody has a remarkable tumor growth inhibition effect. According to the invention, the application range of the fusobacterium specific antibacterial peptide is expanded, and the fusobacterium specific antibacterial peptide has important significance for developing a novel anti-tumor pharmaceutical composition and establishing a novel efficient immunotherapy method.

The invention relates to the technical field of biological medicines, and particularly discloses an mRNA delivery system for targeting dendritic cells as well as a preparation method and application of the mRNA delivery system. The mRNA delivery system is prepared by packaging tumor antigen mRNA into nano-lipid particles (LNP) and coupling the LNP with a specific antibody, and the mRNA delivery system remarkably improves the accuracy and effectiveness of immunotherapy through a'protection-targeting-activation 'triple mechanism, thereby providing technical support for realizing safer and more efficient anti-tumor immunotherapy clinically. On the basis, the invention further provides a vaccine for treating melanoma, and the vaccine has the effects of obviously promoting activation and maturation of DC cells, activating T cells in lymph nodes of a tested body in a tumor microenvironment, obviously improving the expression quantity of melanoma antigen mRNA in the spleen and the like. The goals of inhibiting the growth of melanoma and prolonging the survival time are achieved. The invention is applicable to the field of preparation of tumor vaccines.

The invention discloses an immune cell with an enhanced anti-tumor effect and a preparation method and application of the immune cell, and experiments show that the CD8 + T cell overexpressed by an SERTAD1 gene can enhance the anti-tumor immunotherapy function of the CD8 + T cell. The SERTAD1 gene overexpression can down-regulate expression of immune checkpoint molecules of CD8 + T cells and up-regulate expression of mRNA of cytokines related to tumor killing, in an MC38-OVA subcutaneous tumor model, Nave CD8 + T cells are extracted from an OT-I mouse to over-express SERTAD1 through virus infection, then in-vivo adoptive operation is performed on the mouse, and it is found that the SERTAD1 overexpression can enhance killing of the CD8 + T cells to the MC38-OVA cells, and the SERTAD1 gene overexpression can be used for inhibiting tumor killing of the MC38-OVA cells. The growth of MC38-OVA tumor cells is inhibited, and the tumor volume and weight of an over-expressed SERTAD1 CD8 + T cell adoptive group are obviously smaller than those of a control group.

The invention discloses preparation and application of a Pl3K mutated tumor cell lysate. A preparation method comprises the following steps: constructing a recombinant vector for expressing an amino acid sequence as shown in SEQ ID No.1; transfecting tumor cells with the recombinant vector to obtain a cell line for expressing Pl3K mutant protein; and culturing the cell line expressing the Pl3K mutant protein, collecting the cells, and cracking to obtain the tumor cell lysate. The tumor cell lysate can be applied to antitumor drugs and T lymphocyte immune activation inhibitors. According to the invention, the PI3K mutant is obtained through proper point mutation, the PI3K mutant can effectively inhibit the activation capability of TCL on T lymphocytes, toxic and side effects caused by excessive activation are avoided, a new adoptive cell immunotherapy method based on TCL component optimization is successfully established, and a new thought and strategy are provided for the field of anti-tumor immunotherapy.

This invention relates to the field of biomedical technology and provides a method for preparing a multifunctional nanocomposite material and its applications. The material exhibits good biocompatibility and can be used as a safe agent for tumor treatment; its preparation is simple, green, and pollution-free; it expands the application of quercetin in anti-tumor immunotherapy; it possesses excellent fluorescence / computed tomography dual-mode imaging performance, which can be used to determine tumor boundaries and achieve precise treatment guidance; it has excellent photothermal and photothermally enhanced catalytic properties, possessing advantages such as minimally invasive and highly efficient treatment with few and controllable toxic side effects; it can effectively treat primary, metastatic, or recurrent head and neck squamous cell carcinoma by activating immunity; and by inducing tumor cells to release 2'3'-cGAMP and preventing its degradation, it efficiently activates the cGAS-STING signaling pathway, ultimately enhancing the anti-tumor immune effect.

The invention discloses a nano composition based on sequential induction and degradation and application thereof, and belongs to the technical field of biological medicine. The nano composition based on sequential induction and degradation provided by the invention comprises first nano particles and second nano particles, the first nanoparticles comprise a first carrier and an STING signal pathway agonist loaded on the first carrier; the second nanoparticle comprises a second carrier, and an E3 ligase ligand and a PD-L1 protein ligand which are loaded on the second carrier; the first nanoparticle and the second nanoparticle are configured for sequential application, and the application time of the first nanoparticle is prior to the application time of the second nanoparticle. By constructing the two functional nanoparticles which are sequentially applied, immunosuppression feedback caused by treatment can be actively intercepted and eliminated, so that tumor drug resistance is effectively reversed, and the anti-tumor immunotherapy effect is remarkably improved.

Provided are a switch element capable of specific response and a lysosome-targeting chimera comprising the response switch. Verification shows that the lysosome-targeting chimera can specifically degrade a target protein contained in tumor cells in a tumor microenvironment without affecting the function of normal cells in the body. Moreover, the lysosome-targeting chimera features simple preparation steps, and can be used for preparing an immune checkpoint blockade drug, thereby improving the effect of tumor therapy, solving the translation problem and the problem of on-target / off-tumor toxicity in the prior art, and facilitating the achievement of efficient and safe anti-tumor immunotherapy.

The invention relates to the field of biomedicine, in particular to a multi-immune checkpoint fusion protein as well as a preparation method and application thereof. The invention discloses a functionalized fusion protein which is composed of two modularized fusion proteins: a first module protein is a targeting module and has the function of a traditional immune checkpoint inhibitor; the second module protein is a sialidase long circulation module and has the function of a sugar immune checkpoint inhibitor; the two modular proteins can be specifically bound by a spy reaction through spontaneously formed covalent bonds. And under the synergistic effect of multi-immune checkpoint inhibition, the compound has an excellent anti-tumor immunotherapy effect.

The present invention belongs to the technical field of biomedicine, and specifically relates to the use of bleomycin or a bleomycin analog in the preparation of an immunoenhancer. Further provided in the present invention are a pharmaceutical combination and the use thereof in the preparation of a drug for treating and / or preventing cancers, wherein the pharmaceutical combination contains bleomycin, a bleomycin analog or a combination thereof, and an anti-tumor immunotherapeutic agent.

The present invention relates to the field of immunotherapy of cancer. In particular, the present invention relates to the role of specific strains of gut bacteria, Akkermansia muciniphila Akkermansia muciniphila ) ibiome016 and ibiome017 in anti-tumor immunity, and provides methods for enhancing the response rate of patients to tumor immunotherapy.

Provided herein are nucleic acids, vectors, viral particles, and nanoparticles for delivering immunogenic cell death executioners, e.g., a N-terminal domain of gasdermin D (GSDMD) and / or a N-terminal domain of Mixed Lineage Kinase Domain Like Pseudokinase (MLKL) to cancer cells. The immunogenic cell death executioners induce necroptosis and pyroptosis, respectively, and are under the control of cancer- (e.g., epithelial cell and / or mesenchymal cell) specific promoters for treating carcinomas (e.g., breast carcinomas).

This invention provides an injectable pH-responsive hydrogel nanoparticle, its preparation method, and its applications, relating to the field of bionanomedicine technology. First, nintedanib, zinc ions, and D780 are self-assembled to prepare nanoparticles (NPs). Then, the nanoparticles are cross-linked with an OP hydrogel to obtain injectable pH-responsive hydrogel nanoparticles (OP@NPs). These OP@NPs not only possess a stable structure and injectability but also achieve efficient drug delivery through a pH-triggered release mechanism. Furthermore, OP@NPs can significantly enhance anti-tumor immune responses and effectively inhibit tumor growth by activating in vivo immune cells, improving lactate metabolism, and enhancing immune cell function. They exhibit potent anti-tumor effects and inhibition of osteosarcoma lung metastasis both in vivo and in vitro. When used in combination with the PD-1 antagonist pembrolizumab, they demonstrate great potential as a sensitizer for anti-tumor immunotherapy. This invention provides innovative strategies and new insights for osteosarcoma immunotherapy.

The invention provides an artificially synthesized flora and application of the artificially synthesized flora in auxiliary cancer immunotherapy. Specifically, the artificially synthesized flora provided by the invention is combined with an immune checkpoint inhibitor, especially a PD-1 inhibitor, so that the tumor treatment effect can be enhanced, even the drug resistance of a host to the immune checkpoint inhibitor can be reversed, and finally the effect of remarkably reducing tumors is achieved; before application, the artificially synthesized flora does not need to use antibiotics to remove original intestinal flora of an application object, and after application, the artificially synthesized flora can colonize and partially proliferate in the intestinal tract and cause overall change of intestinal flora composition. The artificially synthesized flora can be used for anti-tumor immunotherapy, improves the response rate of tumor immunotherapy people, and has a potential clinical application prospect.

The invention relates to the technical field of esophageal squamous cell carcinoma immunotherapy, in particular to a nucleic acid coupling drug and application thereof in preparation of antitumor drugs. The invention relates to a nucleic acid coupling medicine, which is prepared from a TLR9 agonist and siRNA (small interfering Ribonucleic Acid) targeting PLD3. According to the present invention, the TLR9 agonist ODN2216 and the siRNA of the targeted PLD3 are coupled through the linker so as to construct the ODN2216-siPLD3 compound; the medicine can be efficiently taken by macrophages, specific knock-down of the PLD3 gene is realized in cells, and meanwhile, a TLR9 signal channel is activated. Experimental results show that the complex not only significantly reduces the PLD3 protein expression level, but also effectively promotes the expression of activation markers CD86 and MHCII of macrophages, which indicates that the complex has the ability of dual regulation and control of TAMs functions, so that the immunosuppression state of the TAMs is reversed, and the anti-tumor immune response is enhanced.

The invention discloses composite paclitaxel albumin nanoparticles as well as a preparation method and application thereof, paclitaxel and a non-nucleotide interferon gene stimulating factor agonist are co-loaded by human serum albumin in a simple manner to form nanoparticles which are uniform in size, proper in particle size, relatively good in dispersity and stable in physicochemical property; the added non-nucleotide interferon gene stimulating factor agonist forms a dimer in a tumor acidic microenvironment, and active targeting of the carrier is combined, so that the nanoparticles have excellent selectivity on tumor tissues; a non-nucleotide interferon gene stimulating factor agonist starts congenital immunity and is combined with adaptive immunity of paclitaxel, so that the defect of low immune responsiveness of'cold 'tumors is overcome. In-vivo and in-vitro toxicity experiments prove that the nanoparticles provided by the invention can solve the problem of strong toxic and side effects of paclitaxel and have synergistic effects on anti-tumor immunotherapy of paclitaxel at the same time, so that the effect of combined treatment is achieved.

The invention discloses a T cell. According to the embodiment of the invention, the expression of Dkk3 in the T cell is up-regulated; or, the expression of Ranbp2 in the T cell is down-regulated. According to the T cell provided by the embodiment of the invention, the expression of an inhibitory receptor can be reduced, the proportion of a precursor Tex can be increased, the function of the T cell can be enhanced, and the depletion of the T cell can be reduced, so that the tumor killing capability and the virus infection removing capability of the T cell can be improved, and support and help can be provided for anti-tumor immunotherapy and virus infection resistance.