38 results about "Immunogenic cell death" patented technology

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.

The present invention provides an immunomodulator for use in the treatment and/or control of a neoplastic disease in a patient intended to undergo immunogenic cell death therapy simultaneously, separately or sequentially with administration of the immunomodulator. The therapy can be selected from microwave irradiation, targeted radiotherapy, embolization, cryotherapy, ultrasound, high intensity focused ultrasound, cyberknife, hyperthermia, radiofrequency ablation, cryoablation, electrotome heating, hot water injection, alcohol injection, embolization, radiation exposure, photodynamic therapy, laser beam irradiation, and combinations thereof.

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 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.

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.

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-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.

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.