2157 results about "T cell" patented technology

The invention discloses a glioma T cell prediction and prognosis evaluation method based on pathological images, particularly relates to the field of patient prognosis health evaluation, and aims to solve the problems that existing pathological evaluation is difficult to combine with tumor structure heterogeneity and immune infiltration distribution, and the future progress risk of a patient cannot be predicted based on follow-up visit pathological data. A spatial heterogeneity map of a tumor core area and an invasion edge is constructed in a digital pathological section, density gradients of T cells in different areas are calculated to generate a distribution heterogeneity coefficient, interaction processing is performed on the two types of characteristics in combination with historical follow-up visit records, and a time sequence neural network constructed based on a gating structure is combined to obtain a high-efficiency characteristic of the tumor. And outputting disease progress probabilities of a plurality of follow-up visit time points in the future to form a prognosis trajectory prediction curve, calculating a quantitative recurrence risk score according to curve slope change and an immune fluctuation mode, and finally generating an individualized management scheme, thereby realizing quantitative prediction evaluation and risk management of the prognosis trend of the glioma patient.

Disclosed herein are antibodies that specifically bind to Gal3 and methods of use thereof. In some embodiments, also described herein are methods of inducing immune activation or promoting T cell or Natural Killer cell proliferation with an antibody that specifically binds to Gal3. Also disclosed herein are methods and compositions of reducing fibrosis or propensity thereof in a tissue with antibodies that specifically bind to Gal3. In some cases, the anti-Gal3 antibody also disrupts the interaction between Gal3 and TIM-3.

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

The invention discloses an application of CD4 + CD8 + double-positive T cells in improvement of poor immune reconstitution of HIV (human immunodeficiency virus) infected patients, and relates to the technical field of biological pharmacy, in particular to the application of preparation of the CD4 + CD8 + double-positive T cells in the poor immune reconstitution of the HIV infected patients. The number of peripheral blood CD4 + T cells of HIV infected patients is increased, the immune system of the patients is improved, and the probability of possible opportunity infection and other related diseases of the patients is reduced, so that the morbidity and mortality of the patients are reduced.

The purpose of the present invention is to provide: a novel therapeutic or prophylactic agent for xerophthalmia; a therapeutic or prophylactic agent for graft-versus-host disease; a corneal epithelium wound healing promoter; a corneal invasive inflammatory cell inhibitor; or an inhibitor of differentiation of lymphocytes into effector T cells. The present invention provides: a therapeutic or prophylactic agent for xerophthalmia, a therapeutic or prophylactic agent for graft-versus-host disease, a corneal epithelial wound healing promoter, a corneal invasive inflammatory cell inhibitor, a tear amount maintenance agent, a corneal epithelial damage inhibitor, and a method for preparing the same, which comprises, as an active ingredient, a substance derived from a stem cell culture supernatant; a cell proliferation marker positive cell inhibitor, or an inhibitor of differentiation of lymphocytes to effector T cells.

Disclosed herein are an engineered immune cell with CD7 gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CD7 gene is designed and synthesized, which can accurately target CD7 gene to achieve gene knock-out with high knock-out efficiency. The provided sgRNA can be used for preparing a CD7-targeting engineered immune cell, and can be further used for preparing a CD7-targeting universal CAR-T cell

Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and / or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

The application provides an application of a FAP-targeted CAR-T cell in preparation of a drug for treating cardiac fibrosis in a chronic phase of myocarditis. It is found in the application that FAP-specific CAR-T cells can effectively target cells expressing mouse FAP proteins, and the CAR-T cells can effectively eliminate cells expressing mouse FAP proteins after being activated, the chimeric antigen receptor T cells effectively reduce cardiac fibrosis in a chronic phase of myocarditis in mice, and restore the function after inflammatory injury. The application develops a CAR-T therapy for myocardial fibrosis caused by a chronic phase of myocarditis, and the chimeric antigen receptor T cells expressing a targeted fibroblast activation protein can recognize activated myocardial fibroblasts, and significantly reduce cardiac fibrosis after inflammatory injury and restore the function.

The present disclosure provides a population of CD4IL-10 / CAR cells (autologous or allogeneic single-donor and allogeneic polydonor) generated by genetically modifying CD4+ Tcells to express IL-10 and a chimeric antigen receptor. Further provided are methods of generating the CD4IL-10 / CAR cells and methods of using the CD4IL-10 / CAR cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and autoimmune and inflammatory disorders.

The invention discloses a fusion protein of a bispecific antibody targeting a T cell and Her2 in series connection with IL-15 and a receptor thereof and an application of the fusion protein. Belongs to the technical field of biology. The fusion protein disclosed by the invention can be combined with a recombinant human CD3 protein and a recombinant human Her2 protein, can be combined with NK92 and SK-BR-3 cell lines, can stimulate NK92 cell proliferation, and can respectively cause ADCC effects mediated by T and NK cells; the antibody has important economic and social significance.

An antigen-binding molecule capable of binding to multiple different antigens (e.g., CD3 on T cells, and CD137 on T cells, NK cells, DC cells, and / or the like), but does not nonspecifically crosslink two or more immune cells such as T cells is provided. Such multispecific antigen-binding molecule is capable of modulating and / or activating an immune response while circumventing the cross-linking between different cells (e.g., different T cells) resulting from the binding of a conventional multispecific antigen-binding molecule to antigens expressed on the different cells, which is considered to be responsible for adverse reactions when the multispecific antigen-binding molecule is used as a drug.

An improved method of treating cancers with engineered T cells is described.

The invention relates to the technical field of biological medicines, in particular to a vaccine for treating or preventing hepatitis B virus infection. The vaccine comprises a hepatitis B surface antigen and a composite adjuvant, wherein the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21, and the composite adjuvant is prepared from CpG oligodeoxynucleotide and saponin QS-21; the nucleotide sequence of the CpG oligodeoxynucleotide is as shown in SEQ ID NO. 1. According to the vaccine provided by the invention, an HBsAg antibody can be generated in a normal mouse body, and HBV in an HBV-carrier mouse can be effectively eliminated, so that the vaccine has the effect of treating or preventing hepatitis B virus infection. According to the vaccine provided by the invention, two adjuvants, namely CpG oligodeoxynucleotide and saponin QS-21, are adopted, so that the vaccine can be used for synergistically activating an immune effect, enhancing the activation of B cells and permanently transforming into plasma cells, and meanwhile, the vaccine can be used for resisting immune tolerance of T cells, realizing the removal of hepatitis B viruses and realizing functional cure of clinical hepatitis B treatment.

The invention discloses a gradient alcohol extraction preparation method of compound honeysuckle flower drops for improving T cell activity, and relates to the technical field of traditional Chinese medicine compound preparations, honeysuckle flower and radix astragali are selected for pretreatment, an ethanol aqueous solution and an interaction regulating agent are added for infiltration, an online traditional Chinese medicine compound preparation HPLC is adopted for dynamic alcohol concentration adjustment and temperature extraction under monitoring of the traditional Chinese medicine compound preparation, the method disclosed by the invention has the advantages that the interaction regulating agent is added in the raw material infiltration stage to block bad interaction among active components, and the online monitoring system is utilized to dynamically adapt the ethanol concentration and the extraction temperature to realize step-by-step efficient dissolution of the multi-polar components; the antioxidant is matched to inhibit oxidation of thermosensitive components, and the solubilizer assists dissolution of insoluble components, so that the core defect that synergistic extraction of multi-polar active components, degradation of the thermosensitive components and interaction inhibition of the components in the compound honeysuckle flowers cannot be considered in the prior art is overcome, and loss or antagonism of the active components is effectively avoided.

The invention discloses a phosphorylated peptidomimetic compound and a medical application thereof. The invention provides a phosphorylated peptidomimetic compound with a novel structure. Activity research shows that the phosphorylated peptidomimetic compound has excellent Cbl-b inhibitory activity and is an effective Cbl-b inhibitor. Technicians in the field know that Cbl-b overexpression can inhibit T cell immune response, and inhibition of Cbl-b can activate killing of an immune system on tumor cells. Therefore, the phosphorylated peptidomimetic compound or pharmaceutically acceptable salts and solvates thereof provided by the invention can be developed and prepared into drugs for treating diseases (such as non-small cell lung cancer, breast cancer, prostate cancer, head and neck squamous cell carcinoma, liver cancer, pancreatic cancer, colorectal cancer, ovarian cancer and other tumors) treated or relieved by inhibiting Cbl-b (such as non-small cell lung cancer, breast cancer, prostate cancer, head and neck squamous cell carcinoma, liver cancer, pancreatic cancer, colorectal cancer, ovarian cancer and the like) the medicine prospect is promising.

Methods for preparing a personalized cancer vaccine and a method to train a machine learning HLA-peptide presentation prediction model. Further wherein, a method of making a HLA class II tetramer or multimer comprising an epitope, the method comprising contacting a purified soluble HLA-DM loaded with a peptide epitope with a HLA class II tetramer or multimer, thereby forming a HLA class II tetramer or multimer loaded with the peptide epitope, is disclosed.

Disclosed in the present invention are a targeted immunotolerance vaccine, a preparation method therefor, and use thereof. The present invention separately modifies a rheumatoid arthritis-related autoantigen peptide and CTLA4 Ig with DSPE-PEG (DP) to prepare a targeted formulation DP-antigen peptide and a targeted formulation DP-CTLA4, which are then mixed to obtain the vaccine. The vaccine described in the present invention, after intravenous injection, binds to albumin in vivo by means of DSPE, "hitchhiking" on albumin to target and enrich in inflammatory lesions, the spleen, the liver, and other tolerance-inducing sites, inhibiting T cell activation, and inducing anergy and apoptosis of rheumatoid arthritis autoantigen-specific T cells, thereby achieving immunotolerance treatment and prevention of rheumatoid arthritis.

The invention belongs to the technical field of biological medicine, and particularly discloses nano composite particles based on a metal organic framework and a preparation method and application of the nano composite particles. The nano-composite particles are constructed through electron adsorption and coordination based on a nano-scale metal organic framework, and under the acidic microenvironment and ultrasonic irradiation of tumors, the nano-composite particles can be decomposed and released in a responsive manner, play a role of a sound-sensitive agent, generate a large amount of active oxygen and induce tumor cells to generate immunogenic death, so that the tumor cell immunogenicity is improved, and the tumor cell immunogenicity is improved. Further, more cytotoxic T lymphocytes are promoted to infiltrate a tumor microenvironment, T cell mediated anti-tumor immune response is recovered, and tumor metastasis is effectively prevented. The carrier metal organic framework ZIF8 of the nano-composite particles can serve as a sound-sensitive agent to generate active oxygen, the function of ultrasonic imaging of tumor tissue can be achieved, the effect of diagnosis is achieved while treatment is conducted, tumor diagnosis and treatment monitoring can be achieved at the same time through one-time drug administration, and a new strategy is provided for precise medical treatment.

The invention discloses a gamma delta T cell efficient amplification method and application, and belongs to the technical field of cell biology. The amplification method comprises the following steps: separating PBMC (peripheral blood mononuclear cells) by adopting a density gradient centrifugation method, carrying out initial culture through a polylysine coated container, carrying out three-stage dynamic stimulation, combining with an X-VIVO 15 culture medium of 5-8% autoserum, and finally carrying out anti-gamma delta TCR magnetic bead separation to obtain high-purity cells. Through collaborative optimization of stepped factor combination, staged container coating and a low-serum system, the amplification multiple of the gamma delta T cells reaches 150-180 times, the purity is larger than or equal to 90% after purification, the cytotoxicity and the survival ability are remarkably improved, the gamma delta T cells can be efficiently used for immunotherapy of tumors and infectious diseases, and stable technical support is provided for clinical transformation of the gamma delta T cells.

The present disclosure features modified immune effector cells (e.g., T cells or NK cells) having increased resistance to inhibition of an immunosuppressive agent relative to unmodified immune effector cells, compositions comprising the same, and methods of using the same.

The present invention is directed to a monoclonal anti-human CS1 clone 7A8D5 antibody or a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 4 and VL having the amino acid of SEQ ID NO: 5. The present invention is also directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) CS1 scFv of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.

Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen / LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

The invention discloses an aptamer-modified lipid nano delivery platform as well as a preparation method and application thereof, and belongs to the field of biomedicine. The platform is prepared by taking DPPC, DOTAP and cholesterol as basic lipid components, Ce6 as a sound-sensitive agent and Flt3L as an immune agonist, controlling the particle size through gradient extrusion, and coupling cholesterol with an EpCAM aptamer for surface modification. The method has the core advantages that active targeting enrichment of tumors is realized by virtue of the aptamer, tumor cell immunogen cell death (ICD) is induced in combination with a sonodynamic therapy (SDT), and damage-related molecular patterns (DAMPs) are released; meanwhile, Flt3L is released in a tumor microenvironment, collection and activation of type 1 classical dendritic cells (cDC1) are specifically promoted, an'endogenous cDC1 vaccine 'is constructed, and CD8 + T cell mediated anti-tumor immune response is enhanced. Experiments prove that the platform can significantly improve the cDC1 infiltration level of a tumor site, effectively inhibit the progress of prostate cancer (PCa), and provide a new normal form for immune'cold tumor 'treatment.

The present invention provides a low pH pharmaceutical composition comprising (a) an antibody constructs comprising a first domain binding to a target cell surface antigen, a second domain binding to a second antigen and preferably a third domain, which is a specific Fc modality, (b) at least one buffer agent, (c) at least one saccharide, and (d) at least one surfactant; and wherein the pH of the pharmaceutical composition is in the range of 3.5 to 6.

The present disclosure provides stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., T cells, B cells, natural killer cells, to genetically modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

The invention provides a gamma delta T cell culture method and a culture medium, and belongs to the technical field of T cell culture. Modified nanoparticles, zoledronic acid, vitamin C and glutamine are added into a 1640 culture solution, the concentration of the modified nanoparticles ranges from 0.5 g / L to 1 g / L, the concentration of the zoledronic acid ranges from 0.5 mu mol / L to 1.5 mu mol / L, the concentration of the vitamin C ranges from 200 mu mol / L to 500 mu mol / L, and the concentration of the glutamine ranges from 0.1 mmol / L to 0.2 mmol / L. The prepared culture medium can efficiently stimulate amplification of the gamma delta T cells and improve the killing activity of the gamma delta T cells, meanwhile, the survival rate of the gamma delta T cells is also improved, and meanwhile, the culture method of the gamma delta T cells is simple, low in cost and wide in application prospect.

The invention relates to the field and discloses application of terahertz waves or intermediate infrared in preparation of adoptive T lymphocytes. The Terahertz wave or mid-infrared modulation technology is utilized to specifically regulate and control the functions of the T cells in a flowing irradiation mode, and the functions of the T cells from different sources are enhanced under the conditions that no medicine is used and no exogenous gene is introduced. Terahertz wave or mid-infrared stimulation is applied to the T cells in a flowing irradiation mode, specific terahertz wave or mid-infrared frequency for remarkably enhancing the functions of the T cells is determined in a frequency screening mode, and after the optimal irradiation frequency is determined, the T cells with the most remarkable function improvement are further input back into a donor. The T cells stimulated by terahertz waves or mid-infrared rays can play a powerful immune function in a tumor microenvironment so as to inhibit further development of tumors.

The present invention provides therapies for the treatment of CCR9 positive cancers, such as T cell acute lymphoblastic leukemia. In particular, the present invention provides a CCR9 targeting moiety. The invention also relates to a CCR9 targeting moiety comprising another targeting moiety, preferably a CD1a targeting moiety, to a dual CAR comprising CCR9 and CD1a targeting moieties, to the use thereof in the treatment of CCR9 and / or CD1a positive cancers, and to the use of a CCR9 targeting moiety and a CD1a targeting moiety alone for such treatments.