38 results about "Immunogenic cell death" patented technology

Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

Anthracyclin-treated turn or cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclins induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

The invention discloses a composite sound-sensitive agent. The composite sound-sensitive agent comprises sound-sensitive agent nanoparticles and oxygen-producing microorganisms, under the irradiation of near-infrared laser, the oxygen-producing microorganisms continuously perform photosynthesis to produce oxygen, so that an anoxic tumor area is subjected to photooxygenation, and the sound-sensitive agent is ultrasonically excited to convert the oxygen into a large amount of singlet oxygen with cytotoxicity, so that tumor cells are effectively killed and tumor tissues are effectively damaged. Immunogen cell death caused by improvement of a tumor hypoxic environment and sonodynamic therapy is realized, and synergistic therapy of sonodynamic and immune is realized. Meanwhile, the composite sound-sensitive agent can be used for magnetic resonance imaging and computed tomography contrast imaging, and real-time monitoring of the sonodynamic therapy process is achieved. The work provides good theoretical and experimental support for development of good biocompatibility and effective sonodynamic force of hybrid microorganisms, and shows important clinical transformation prospects in sonodynamic force of microbial nano medicine.

An improved autovaccination method designed to prevent or treat various neoplastic diseases by inducing a systemic immune response against a tumor and its remote metastases, consisting of the induction of an immunogenic cell death in one or more targeted tumor sites with local radiation therapy, cryotherapy, heat, chemotherapy or various other treatments, followed by intratumoral / peritumoral injection of dsRNAs (poly-ICLC in particular) in the same tumor site.

A method for increasing the progression free survival or overall survival of a patient with cancer comprising: determining if the cancer has a surrounding microenvironment that is favorable to immune modulation; determining if the chemotherapy regimen induces immunogenic cell death, and if both are yes, administering an effective amount of a CDK 4 / 6 inhibitor selected from Compounds I, II, III, IV, or V, or a pharmaceutically acceptable salt thereof, wherein the CDK4 / 6 inhibitor is administered prior to the administration of the chemotherapy or optionally prior to and concurrently with chemotherapy; and, wherein the increase in progression free survival or overall survival is in comparison to the progression free survival or overall survival based on administration of the chemotherapy alone, either based on literature or otherwise publicly available evidence, a comparative during preclinical or clinical trials, or other means accepted by persons skilled in the field.

The invention relates to a photosensitizer for inducing death of immunogenic cells and a preparation method and application thereof, and belongs to the technical field of medicines. The photosensitizer is a polyphenyl pyrrole derivative (named as MAP-I) containing a D-pi-A structure, triphenylamine is introduced to the 2, 5-site of pyrrole to serve as a substituent group, indole salt is introduced to the 3-site of pyrrole to serve as a targeting agent of mitochondria, and then heavy atom iodine is introduced to a receptor group of a molecule to obtain the photosensitizer. The photosensitizer has the functions of high active oxygen generation rate, stimulation of cells to generate damage-related molecular patterns, in-vitro induction of dendritic cells and induction of in-vivo immunogenic cell death process of organisms, and can be applied to the field of cancer treatment.

The invention provides a pharmaceutical composition for mild photothermal therapy of tumors as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition is composed of a dual-targeting amphiphilic glucan derivative carrier, a material (PTA) with photo-thermal conversion performance and an autophagy inhibitor. The dual-targeting amphiphilic glucan derivative carrier can be self-assembled in water to form nano-micelles, and is physically loaded with PTA and an autophagy inhibitor for tumor photothermal therapy. The preparation is mainly characterized in that: 1) the preparation has active dual-targeting capability of tumor cells and tumor-related fibroblasts, and can efficiently enter the cells through the action of receptor ligands, so that the transfer efficiency of the preparation is improved; 2) under the irradiation of 808nm laser, PTA absorbs light energy and efficiently converts the light energy into heat, and the autophagy inhibitor inhibits the autophagy behavior of tumor cells and sensibilizes photo-thermal, so that an excellent mild photo-thermal treatment effect is realized, and the physical barrier of a tumor matrix can be weakened; tumor photothermal can further induce tumor cells to generate immunogenic cell death, generated tumor fragments can further activate an immune system, and the tumor photothermal treatment effect is greatly improved.

The invention discloses a new medicinal application of effective components and derivatives in Glycyrrhiza uralensis. The effective components and derivatives in Glycyrrhiza uralensis include liquiritin, glycyrrhizin, glycyrrhetinic acid, isoliquiritigenin, licochalcone A, glycyrrhizic acid and its derivative glycyrrhizic acid monoammonium salt, and the effective components and derivatives in Glycyrrhiza uralensis are used for preparing anticancer drugs. As that effective component in Glycyrrhiza uralensis and its derivative can induce tumor cells to produce immunogenic cell death. The invention provides a tumor treatment drug with definite curative effect, safety, convenience and wide sources, which can be combined with one or more pharmaceutically acceptable carriers or excipients to prepare pharmaceutical compositions or preparations of active components in licorice and derivatives thereof, it provides new drugs for tumor immunotherapy and is of great significance for improving tumor therapeutic effect and quality of life of patients. The effective components come from fruits, vegetables and medicinal materials, with small side effects, low cost and convenient popularization anduse.

The invention discloses a manganese-based radiotherapy sensitizer. The manganese-based radiotherapy sensitizer is a pegylation hollow manganese oxide nanoparticle material loaded with a small molecule PI3K gamma kinase inhibitor; wherein the small molecule PI3K gamma kinase inhibitor is IPI549 (Institute of Phosphorus Institute 549). The invention also provides a preparation method of the manganese-based radiotherapy sensitizer and application of the manganese-based radiotherapy sensitizer in preparation of tumor therapeutic agents. The manganese-based radiotherapy sensitizer disclosed by the invention has dual functions of radiotherapy sensitization and immunoregulation, and can be applied to inhibition of remnant tumor recurrence; the manganese dioxide nanoparticles are degraded in an acidic tumor microenvironment, so that responsive drug release at a tumor site is realized, and radiotherapy of postoperative hypoxia relief can be realized; pI3K gamma inhibition radiotherapy-mediated immunogenic cell death effects are synergistic, so that after excision, the immunosuppressive TME is reprogrammed into an immunogenic phenotype, and meanwhile, the susceptibility of blocking treatment on an immune checkpoint is improved. Radiotherapy based on the manganese-based radiotherapy sensitizer is combined with PD-L1 blocking, so that local residual tumors and distant metastatic tumors can be remarkably inhibited, and tumor re-inoculation can be prevented.

Use of (pyrophosphato)platinum(II) or platinum(IV) complexes (“phosphaplatins”), especially 1,2-cyclohexanediamine(pyrophosphato) platinum(II), as immunogenic cell death (ICD) inducing agents and their combination with immune checkpoint protein inhibitors for treatment of cancers, and the mechanistic rationale for the methods thereof, are disclosed.

The invention discloses a composite nano material based on ferrocene and hypericin as well as a preparation method and application of the composite nano material. The preparation method comprises the following steps: adding polyethylene glycol polylysine, ferrocenecarboxylic acid N-succinimide ester and hypericin into a tetrahydrofuran medium, and self-assembling the product to form the composite nano material based on ferrocene and hypericin. The prepared composite nano material based on ferrocene and hypericin has the advantages of being high in local concentration, good in anti-tumor curative effect, rapid in kidney clearance, high in biocompatibility, small in toxic and side effects and the like. The good anti-tumor curative effect is reflected in that a large amount of active oxygen is generated, glutathione on the local part of a tumor is depleted, ferroptosis and hypericin-mediated photodynamic therapy generate a synergistic effect, meanwhile, immunogenic cell death is triggered, and the powerful anti-tumor effect is achieved.

There is provided a method of increasing progression-free lifetime or overall lifetime of a cancer patient, comprising: determining whether the cancer has an ambient microenvironment that facilitates immunomodulation; determining whether the chemotherapy regimen induces immunogenic cell death, and if both are so, administering an effective amount of a CDK4 / 6 inhibitor selected from Compound I, II, III, IV or V or a pharmaceutically acceptable salt thereof wherein the CDK4 / 6 inhibitor is administered prior to administration of chemotherapy or optionally prior to and concurrently with chemotherapy; and wherein the increase in progression-free lifetime or overall lifetime is compared to progression-free lifetime or overall lifetime based on the administration of chemotherapy alone, said comparison being based on evidence available in documents or otherwise disclosed, comparisons during preclinical or clinical trials, or other means accepted by those skilled in the art.

Contemplated compositions and methods counteract evasive measures of a tumor by rendering access to the tumor microenvironment, tagging the tumor microenvironment with chemoattractant and / or cytokines, delivering or facilitating a cell-based therapy in the tumor microenvironment while providing inhibition of immune suppressor cells in the tumor microenvironment.

The invention discloses combined medicine capable of simultaneously amplifying immunogenic cell death and enhancing an anti-tumor effect. The anti-tumor combined medicine comprises a cardiac glycosidecompound used as an active ingredient and a cytotoxic N-(2-hydroxypropyl) methacrylamide HPMA polymer medicine conjugate, wherein the cardiac glycoside compound is at least one of clinical medicine including digoxin, digitonin, deacetylated erioflorin, erioflorin C, G erioflorin, oleandrine and erioflorin K. The cytotoxic HPMA polymer medicine conjugate is an HPMA conjugate carrying at least oneof cis-platinum, carboplatin, nedaplatin, oxaliplatin, lerplatinum and heptplatinum. According to the invention, the cardiac glycoside compound and the N-(2-hydroxypropyl) methacrylamide HPMA polymermedicine conjugate are combined for use, so that the capability of causing anti-tumor immune response is improved, and the anti-tumor effect is enhanced.

The invention provides a bovine serum albumin-tea polyphenol molybdenum nano-composite, and belongs to the field of nano-medicine. The bovine serum albumin-tea polyphenol-molybdenum nano-composite is prepared by dissolving bovine serum albumin in water, dropwise adding a tea polyphenol aqueous solution and a molybdenum source aqueous solution, dropwise adding a sodium hydroxide aqueous solution, and reacting by adopting a biomineralization method to obtain the bovine serum albumin-tea polyphenol-molybdenum nano-composite. The invention also provides application of the bovine serum albumin-tea polyphenol molybdenum nano-composite in preparation of drugs for treating cancer cell immunogenic cell death and tumor immunotherapy. The composite provided by the invention has good biocompatibility, good dispersibility in water and good capability of triggering mouse cancer cell immunogenic cell death, and can be effectively applied to immunotherapy of tumors.

The invention relates to the field of organic synthesis and biological medicine, particularly to synthesis of a class of photosensitizers with aggregation-induced emission properties, and applicationof the photosensitizers loaded on a solid-phase material in synthesis of bioactive molecules or medical intermediates and application of the photosensitizers in the medical fields of photodynamic therapy, immunogenic cell death and the like. According to the invention, the photosensitizer can effectively generate singlet oxygen under an illumination condition; compared with the traditional photosensitizer, the photosensitizer of the invention has the following characteristics that the phenomena of aggregation fluorescence quenching and aggregation singlet oxygen generation capacity reduction are avoided; and when the photosensitizer is applied to synthesis of bioactive molecules or medical intermediates, the photosensitizer has the advantages of reusability, simple and convenient post-treatment and the like, and the characteristics are not possessed by traditional photosensitizers.

The invention discloses a pharmaceutical composition for bladder perfusion. The pharmaceutical composition comprises soluble salt of an immunologic adjuvant and a chemical drug capable of causing death of immunogenic cells. Pharmaceutical compositions useful in or for the treatment of bladder cancer. When the soluble salt of the immunologic adjuvant is combined with a chemical drug capable of causing death of immunogenic cells as a bladder perfusion drug, the side effect of the chemical drug can be reduced, a synergistic anti-cancer effect can be generated, the cancer metastasis and recurrence probability can be reduced, and the existence of the immunologic adjuvant promotes a large number of macrophages to be enriched around tumor tissues of the bladder, so that the cancer metastasis and recurrence probability can be reduced. After the ICD drug plays a role in initial chemotherapy and immune excitation, macrophages can swallow a large number of tumor extracellular free chemotherapeutic drugs, and damage of the chemotherapeutic drugs to normal tissues can be reduced, so that systematic toxic and side effects of ICD chemical drugs are reduced.

Anthracyclines induce the rapid, pre-apoptotic translocation of ERP57 to the cell surface. Knock down of ERP57 inhibit the translocation of CRT, suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. In contrast, the blockade of ERP57 with blocking antibody had no effect on phagocytosis of anthracyclines-treated tumor cells by dendritic cells and their immunogenicity in mammals, such as mice. The anthracyclines-induced ERP57 translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant ERP57 did not restored the immunogenicity of cell death elicited by etoposide and mitomycin C, or enhanced their antitumor effects in vivo in contrast to the administration of recombinant CRT. These data identify the presence of ERP57 crucial for the translocation of CRT and to induce immunogenic cell death which will activate a anti-cancer immune responses.

Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

The present invention generally relates to systems and methods for treating cancer using immunogenic cell death, e.g., lysosome-induced immunogenic cell death. This includes at least three aspects, which may be used separately or together. A first aspect involves the preparation of a tumor for treatment, for example, by withdrawal and suppression of antioxidants, supply of n-3 through n-6 and other unsaturated fatty acids, and / or treatment of the subject with statins. A second aspect involves restoration of p53 functionality through genetic manipulation, including techniques involving CRISPR.A third aspect involves constructing an antibody-enzyme complex where the antibody recognizes the tumor and the enzyme is an oxidase. The complex may be administered to a subject. The subject may alsobe provided with a substrate to the enzyme. These and / or other aspects, may be used separately or together, and may be used to treat and / or cure cancer. In some cases, the lysosome may be targeted ininducing cell death, e.g., in cancer cells.

Use of (pyrophosphato)platinum(II) or platinum(IV) complexes (“phosphaplatins”), especially 1,2-cyclohexanediamine(pyrophosphato) platinum(II), as immunogenic cell death (ICD) inducing agents and their combination with immune checkpoint protein inhibitors for treatment of cancers, and the mechanistic rationale for the methods thereof, are disclosed.

The invention belongs to the field of biomedical macromolecules, and discloses a tumor-mitochondria double-targeting polymer as well as a preparation method and application thereof. According to the invention, a polymer modified by a light absorber CSMA is used for preparing nano particles through a self-assembly method; the light absorber CSMA has a function of targeting mitochondria; a light absorber CSMA in the particles, when being triggered by an external trigger source, can absorb energy and generate heat, wherein the generated heat can cause damage to mitochondria of the tumor and immunogenic cell death; the tumor antigens released by immunogenic tumor cell death and injury-related mode molecules can be further combined with immune activators loaded in the nanoparticles to serve aspersonalized vaccines, so that an organism immune system is activated to kill tumors and inhibit tumor growth for a long time, and good biological treatment prospects are achieved.

Disclosed are micellar formulations comprising a synergistic combination of quercetin and alantolactone and their use for treating a cancer, including microsatellite-stable colorectal cancer (CRC), which otherwise is resistant to immunotherapy. The combination of quercetin and alantolactone was found to induce synergistic immunogenic cell death (ICD) at synergistic ratiometric micellar loadings.

The invention provides application of an immunogenic cell death-related gene in survival prognosis and radiotherapy responsiveness of head and neck squamous carcinoma, and belongs to the technical field of disease prognosis and molecular biology. According to the application, the immunogenic cell death-related gene prognostic index (ICDRGPI) is constructed by screening the head and neck squamous carcinoma prognosis-related gene, and the ICDRGPI is proved to have a good prediction effect on the survival of head and neck squamous carcinoma patients; and the survival of the ICDRGPI is obviously different from that of the patients after radiotherapy, and the ICDRGPI can be used for prognosis prediction of the head and neck squamous carcinoma patients and can assist clinical radiotherapy decision-making, so that the application has good practical application value.

The present invention relates, in part, to methods of inducing immunogenic cell death to treat a cancer in a subject comprising administering to the subject a therapeutically effective amount of an agent that increases one or more biomarkers listed in Table 1 in combination with an inducer of immunogenic cell death (ICD).

The disclosure provides a method for removing a cancer tumor stem cell and then further removing a tumor cell and provides an application of a drug molecule and its preparation in tumor treatment or prevention. On the one hand, by inducing the death of immunogenic cells, the anti-tumor immune response is enhanced. On the other hand, indoleamine-2,3-oxygenase is inhibited, immune cells, cytokines, amino acids, etc. are regulated, which improves the niche of cancer stem cells and makes them no longer conducive to the growth of cancer stem cells. Stem cell dormancy is lifted, and the sensitivity of cancer stem cells to chemotherapy drugs and immune cells is enhanced, so that cancer stem cells and tumor cells are effectively killed, and the efficacy of tumor treatment is improved.

The invention provides a nucleic acid nano-drug carrier as well as a preparation method and application thereof. The nucleic acid nano-drug carrier comprises a DNA origami nano-structure, a cholesterol-disulfide bond-DNA compound, a tumor targeting peptide-DNA compound and a drug, and the origami structure contains a response element DNA molecular lock modified with a disulfide bond. The nucleic acid nano-drug carrier provided by the invention can deliver a chemotherapeutic drug to a tumor site in a targeted manner, responds to a tumor environment, opens the carrier to release the chemotherapeutic drug, reduces toxic and side effects of the chemotherapeutic drug on normal tissues and organs, triggers tumor cell immunogenic cell death, and activates anti-tumor immunity. And by combining with an immune checkpoint antibody, the aim of better treating tumors is fulfilled.