116 results about "Cytotoxic T cell" patented technology

The present invention relates to: a method for evaluating the efficacy of an anti-cancer drug, a method for screening an anti-cancer drug, a system for evaluating the efficacy of an anti-cancer drug, or a system for screening an anti-cancer drug, using a mixture of peripheral blood mononuclear cells (PBMC) and a cancer organoid. Specifically, the present invention relates to: a method for evaluating the efficacy of an anti-cancer drug, a method for screening an anti-cancer drug, a system for evaluating the efficacy of an anti-cancer drug, or a system for screening an anti-cancer drug, using a mixture of cytotoxic T cells differentiated from PBMC and cancer organoids. According to the method for evaluating the efficacy of an anti-cancer drug, the screening method, the efficacy evaluation system, or the screening system of the present invention, a tumor microenvironment, i.e. The form in which cancer cells are present in a living body, can be very closely reproduced. Furthermore, since PBMCs derived from normal individuals are used and differentiated into cancer patient-specific cytotoxic T cells, the burden of collecting biological samples such as blood and tissue samples from cancer patients can be reduced, and the efficacy of an anti-cancer drug can be evaluated with high accuracy.

The invention discloses a preparation method and application of porcine pseudorabies virus multi-epitope polypeptide, and belongs to the technical field of veterinary biological products. The multi-epitope polypeptide comprises a cytotoxic T cell epitope, a helper T cell epitope and a linear B cell epitope; the cell epitopes are screened from key immunogenic proteins of the pseudorabies virus by using an immunoinformatics method. The porcine pseudorabies virus multi-epitope polypeptide designed by the invention is high in safety, has better antigenicity and physicochemical properties, can be efficiently expressed, and can be recognized by a pseudorabies virus specific antibody. By applying the porcine pseudorabies virus multi-epitope polypeptide, high-level specific antibodies and cellular immune response can be continuously induced to generate, strong protective efficacy is generated, and mice can be protected from death when infected with a lethal dose of porcine pseudorabies virus. Therefore, the multi-epitope polypeptide disclosed by the invention can be used as an alternative antigen of a porcine pseudorabies virus vaccine, the use of active virus is avoided, and a tool is provided for eradication of porcine pseudorabies virus.

The invention discloses an application of a small molecular compound LZ-A4 in preparation of a preparation or a medicine for treating malignant tumors. The chemical formula of the small molecule compound LZ-A4 is C19H11Cl2N3O3S, and the small molecule compound LZ-A4 can promote degradation of LGMN in malignant tumor cells, inhibit proliferation of tumor cells and inhibit polarization of macrophages to M2 type. The research on a colorectal cancer mouse transplantation tumor model proves that the development of the colorectal cancer can be effectively inhibited by single treatment of the LZ-A4, and the volume of the tumor can be further reduced after the LZ-A4 is combined with a clinical first-line chemotherapeutic drug Oxaliplatin for the colorectal cancer. Meanwhile, the LZ-A4 can inhibit M2 type polarization of macrophages in a tumor microenvironment in vivo, promote infiltration of cytotoxic T cells, remodel the tumor microenvironment and activate anti-tumor immunity. In addition, the A4 has good toxic and side effects, and does not cause further reduction of the body weight of the mouse after being combined with chemotherapeutic drugs.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The invention provides a rapid detection method for cytotoxic T cells in peripheral blood. Specifically, the method provided by the invention is used for rapidly identifying the cytotoxic T cells in the peripheral blood by detecting the expression of cell surface proteins CX3CR1 and GPR56. The method provided by the invention is quick to operate, does not involve cell fixation and membrane rupture, and does not affect cell activity.

Provided herein, among other things, is a cytotoxic immune cell (e.g., a cytotoxic T cell) that expresses an engineered immune receptor (such as a CAR or TCR) whose cytotoxicity within the tumor microenvironment is enhanced by a pro-inflammatory protein that is induced only when the cell binds to either a tissue-specific or cancer-associated antigen. As such, the present cells can be used for the treatment of cancers that are associated with solid tumors.

The invention belongs to the field of biological medicine, and relates to a method for preparing iTNK cells, prepared iTNK, a pharmaceutical composition of the iTNK and application of the iTNK. Specifically, the invention relates to a method for preparing iTNK cells, which comprises the following steps: (1) adding a proper amount of anti-CD3 / CD28 / CD2T cell Activator into a culture medium for culturing T cells; culturing for 1-4 days; preferably culturing for 2 days; (2) replacing the culture medium with a culture medium which does not contain anti-CD3 / CD28 / CD2T cell Activator, and continuously culturing for 20 to 30 days; preferably, the culture lasts for 26 days. The iTNK cell prepared by the method disclosed by the invention has dual attributes of cytotoxic T cells and NK cells and a tumor killing function, and has a good anti-tumor application prospect.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

The invention discloses an elephant source bacillus licheniformis and application thereof. The preservation number of the bacillus licheniformis strain L517 is GDMCC 67825, the bacillus licheniformis strain L517 is classified and named as bacillus licheniformis, and the preservation date is February 26, 2026. Research finds that the bacillus licheniformis has a remarkable treatment effect on acute colitis of mice; and the traditional Chinese medicine composition also has a remarkable treatment effect on mouse subcutaneous colon cancer. The anti-cancer mechanism is that the infiltration of GZMB < + > CD8 < + > cytotoxic T cells in a tumor microenvironment is remarkably promoted in vivo through a supernatant metabolite of a culture medium, and a tumor suppressor gene P53 can be directly up-regulated. It is found for the first time that the elephant intestinal tract source bacillus licheniformis with evolutionary disease-resistant advantages shows good anti-proctitis and colon cancer activity, and can become an effective medicine for treating proctitis and colon cancer in the future.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APCs.

To provide a novel chimeric antigen receptor-T cell (CAR-T cell) therapy, and to provide a medicament using the same.SOLUTION: Provided are: a method for producing T cell-derived induced Pluripotent Stem Cells (T-iPSCs) with two antigen receptors, comprising introducing, into cytotoxic T lymphocyte (CTL)-derived iPS cells (T-iPSCs) specific to a tumor antigen or viral antigen expressed on target cells, a chimeric antigen receptor (CAR) specific for an antigen different from the antigen; T-iPSCs with a T cell receptor (TCR) specific to a tumor antigen or viral antigen expressed on target cells and a CAR specific to an antigen different from the antigen; and furthermore, CTLs expressing a TCR specific to a tumor antigen or viral antigen expressed on target cells and a CAR specific to an antigen different from the antigen.SELECTED DRAWING: None

The present invention provides KOC1-derived epitope peptides having the ability to induce cytotoxic T cells. The present invention also provides polynucleotides encoding the peptides, antigen-presenting cells presenting the peptides, and cytotoxic T cells targeting the peptides, as well as methods for inducing antigen-presenting cells or CTLs. The present invention also provides compositions and pharmaceutical compositions containing them as active ingredients. In addition, the present invention provides methods for treating and / or preventing cancer, and / or preventing its postoperative recurrence using the peptides, polynucleotides, antigen-presenting cells, cytotoxic T cells or pharmaceutical compositions of the present invention. A method for inducing an immune response against cancer is also provided.

A nanoparticle and a preparation method therefor, the nanoparticle including an amphiphilic peptide, which forms a micelle structure through self-assembly, and a target peptide (preferably, a water-soluble antigen peptide), which electrically binds to the surface of the amphiphilic peptide. The target peptide electrically binds to the surface of the amphiphilic peptide micelle structure and becomes particulated, and thus can be effectively presented to an antigen-presenting cell, and the weight ratio of the amphiphilic peptide and the target peptide is controlled so that the size of nanoparticles is controlled and endocytosis thereof is carried out, and thus immunity by means of cytotoxic T cells can be induced. Nanoparticles exhibit use only an epitope of a more accurate region so as to be effective as a vaccine, and thus have minimal side effects. Therefore, excellent antigen-specific antibody and cell immunotherapy effects are exhibited, and thus can be used in various fields such as vaccine production.

CD38 is also expressed in a variety of hematological malignancies, including multiple myeloma. In the present invention, the inventors obtained a new antibody against CD38 that can be used to produce bispecific antibodies and CAR T cell populations. In particular, the inventors reported the development of Bi38-3, a new bispecific T cell engager that targets CD38 on MM cells and forms cytotoxic T cells through CD3ε. Bi38-3 lacks the Fc region of natural mAbs, which contributes to the resistance process, but triggers T cell proliferation, cytokine release, and lysis of CD38-positive MM cells in vitro. Similarly, Bi38-3 induces autologous T cells to eliminate tumor plasma cells isolated from MM patients at diagnosis and relapse. The cytotoxicity triggered by Bi38-3 is limited to cells expressing high levels of CD38 and maintains the integrity of T, B, and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in the MM1.S xenograft mouse model of human MM. In summary, the results show that the antibody of the present invention is an effective agent for specifically eliminating CD38-positive malignant cells without significantly affecting CD38-low-expressing cells, and is a promising new immunotherapy tool for treating malignant blood diseases, especially multiple myeloma.

The present invention relates to the field of medical materials technology, and in particular to an anti-tumor vaccine and its applications. The anti-tumor vaccine comprises anti-tumor nanoparticles comprising a nucleic acid encoding a plasma membrane vesicle-associated protein (PLVAP), a cationic lipid, and a non-cationic lipid. Research has shown that an anti-tumor vaccine based on an antigen molecule specifically expressed on tumor vascular endothelial cells (PLVAP) can effectively activate the immunosuppressive microenvironment of tumor patients, inducing the generation of a large number of cytotoxic T cells. These T cells are capable of targeting and killing tumor vascular endothelial cells expressing the PLVAP protein, effectively destroying tumor blood vessels. This vaccine holds significant value in the field of anti-tumor biomaterials.

A bispecific antibody, including: a first antibody or antigen-binding fragment thereof that specifically binds to a first antigen; a second antibody or antigen-binding fragment thereof that specifically binds to a second antigen; where the first antigen is TNFR2, and the second antigen is 4-1BB; or, the first antigen is 4-1BB, and the second antigen is TNFR2. The bispecific antibody is a T cell regulator of the tumor microenvironment, which can stimulate the proliferation of CD8+T cells, activate CD8+T cells, and release anti-tumor factors, such as IFNγ and IL2 by using a TNFR2 agonistic antibody, or can block TNF-TNFR2 and inhibit the proliferation of Treg by using a TNFR2 antagonistic antibody. The bispecific antibody can simultaneously target 4-1BB, activate the 4-1BB signaling pathway of T cells and NK cells, enhance the killing power of cytotoxic T cells and NK cells, and produce anti-tumor activity.

The invention discloses an application of an esterase response cationic polymer in preparation of an anti-tumor immunotherapy drug. The esterase response cationic polymer is an esterase response cationic polymer containing (p-phenolic ester group) benzyl amine or (p-phenolic ester group) benzyl ester. The compound can kill tumor cells, induce immunogen cell death (ICD), promote the tumor cells to release tumor-associated antigens, induce antigen-presenting cells to gather in tumors and present tumor antigens, activate killer T cells, inhibit tumor neovascularization, improve the tumor microenvironment, inhibit tumor cell apoptosis, inhibit tumor cell apoptosis, inhibit tumor cell apoptosis and inhibit tumor cell apoptosis after intratumor injection. Therefore, the organism obtains the anti-tumor immunity capability.

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 30 peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The present invention relates to a composition, for prevention or treatment of cancer diseases, comprising CD8+ T cells activated by CD4+ T cell-derived extracellular vesicles as an active ingredient. It was found that the secretion of extracellular vesicles from cytokine-activated CD4+ T cells increases and the extracellular vesicles enhance proliferation and activity of CD8+ T cells to induce the death of cancer cells, thereby augmenting an anticancer effect. Thus, the present invention provides the CD8+ T cells activated by CD4+ T cell-derived extracellular vesicles as a pharmaceutical agent or an immunotherapeutic agent for cancer diseases, and a method for activating CD8+ T cells by using CD4+ T cell-derived extracellular vesicles to prepare CD8+ T cells showing excellent anticancer activity as described above.

The invention discloses an antigen peptide combination associated with liver cancer driver gene mutations, wherein the liver cancer driver genes are ERBB4, HNF1A, LRP1B, PREX2 and ZNF521; the sequences of the antigen peptide combination are SEQ ID NO.3, SEQ ID NO.5, SEQ ID NO.6, SEQ ID NO.11, SEQ ID NO.14 and SEQ ID NO.15; application of the antigen peptide combination, using the antigen peptide combination to induce specific cytotoxic T cell clones; the antigen peptide combination has a high affinity with MHC I molecules on DC cells, can effectively stimulate and induce the generation of specific cytotoxic T lymphocytes, can be used for immune clearance of tumor cells with liver cancer-related driver gene mutations, and has good therapeutic potential.

The present technology provides compositions and methods for modulating T Cell Receptor (TCR) specificity as well as methods for treating cancer in a subject in need thereof. The present disclosure provides engineered cytotoxic T cells comprising a TCR and / or nucleic acid encoding the TCR and a mutant CD8 alpha polypeptide and / or nucleic acid encoding the mutant CD8 alpha polypeptide.

A rapid detection method for cytotoxic T cells in peripheral blood. The method enables rapid identification of cytotoxic T cells in peripheral blood by detecting the expression of T-cell surface protein CX3CR1, or CX3CR1 and GPR56. The detection method is rapid in operation, does not involve cell fixation and permeabilization, and does not affect cell activity.

Provided is a method for evaluating the efficacy of an anticancer drug using a mixture of peripheral blood mononuclear cells and cancer organoids; a method for screening the anticancer drug; a system for evaluating the efficacy of the anticancer drug; or a system for screening the anticancer drug. Specifically, the present invention relates to: a method for evaluating the efficacy of an anticancer drug using a mixture of cytotoxic T cells differentiated from PBMCs and cancer organoids; a method for screening the anticancer drug; a system for evaluating the efficacy of the anticancer drug; or a system for screening the anticancer drug. The method for evaluating the efficacy of an anticancer drug, the screening method, the efficacy evaluation system, or the screening system according to the present invention can very closely reproduce a tumor microenvironment, which is the form in which cancer cells exist in a living body.

Provided is a composition for cytotoxic T cell depletion, comprising an anti-LAG-3 antibody or a binding fragment thereof having the properties described in (i) to (iii) below: (1) having in vitro ADCC activity; (ii) reducing, in a low fucose form, the number of LAG-3 positive cells in vivo; and (iii) binding to activated human T cells. Also provided are methods for depleting cytotoxic T cells using the disclosed anti-LAG-3 antibody or binding fragment thereof.

Disclosed is a method for producing activated cytotoxic T cells derived from iPS cells, the method comprising the following steps (1): (1) activating non-activated cytotoxic T cells derived from iPS cells in a container having excellent gas exchange performance; a method for proliferating activated cytotoxic T cells derived from iPS cells, the method comprising the following steps (1A): (1A) activating non-activated cytotoxic T cells derived from iPS cells in a container having excellent gas exchange performance; a cell population comprising the activated cytotoxic T cells obtained by the method; and a drug comprising the cell population comprising the activated cytotoxic T cells.

The present invention discloses an antigen peptide combination associated with liver cancer driver gene mutations, wherein the liver cancer driver genes are NFE2L2 and PREX2; the sequences of the antigen peptide combination are SEQ ID NO.8 and SEQ ID NO.13; application of the antigen peptide combination, wherein the antigen peptide combination is used to induce the production of specific cytotoxic T cell clones; the antigen peptide combination has a high affinity with MHC I molecules on DC cells, and can effectively stimulate and induce the production of specific cytotoxic T lymphocytes, and can be used for immune clearance of tumor cells with liver cancer-related driver gene mutations, and has good therapeutic potential.

The purpose of the present invention is to provide a cancer vaccine composition effective for treating or preventing cancer. The present invention provides a genetically modified cancer cell comprising: a nucleic acid encoding a cytotoxic T cell-inducing antigen and a nucleic acid encoding IL-2. This genetically modified cancer cell can be used as an active ingredient of a cancer vaccine composition. The cytotoxic T cell-inducing antigen in this genetically modified cancer cell is preferably a pathogen-derived antigen or a virus-derived antigen.

A method for generating antigen-specific CD4+ cytotoxic T cells comprising providing a plurality of CD4+ T cells; stimulating the CD4+ T cells with at least one tumor associated-antigen (TAA) peptide and / or at least one viral peptide; and expanding the CD4+ T cells in the presence of at least one pro-inflammatory cytokine. Also provided are enriched populations and compositions comprising the generated antigen-specific CD4+ cytotoxic T cells, and methods of treating, ameliorating, or preventing cancers and disease by administering the cells to subjects.

The invention relates to application of a dry memory T cell in preparation of a medicine for treating colorectal cancer pulmonary metastasis, and belongs to the technical field of biological medicine. The invention firstly proves that the capability of differentiating the Tscm cells into effector killer T cells can be effectively improved by knocking out the Erbin genes in the Tscm cells in a mouse body, lung metastasis of colorectal cancer is inhibited, and the treatment effect of CAR-T cells can be enhanced by the Tscm cells with the Erbin genes knocked out. In addition, xanthine is detected for many times in a mouse colorectal cancer lung metastasis focus after the Erbin gene in the Tscm cell is knocked out, hypoxanthine can promote generation of more Tscm cells in the tumor metastasis focus, and the Tscm cells are differentiated to generate killer T cells, so that colorectal cancer lung metastasis is inhibited. The metabolic pathway of hypoxanthine is further studied, it is found that allopurinol can inhibit conversion of hypoxanthine into xanthine and uric acid, and it is found that allopurinol can also inhibit colorectal cancer lung metastasis by injecting allopurinol into a colorectal cancer lung metastasis mouse model.