42408results about "Antineoplastic agents" patented technology

The disclosure provides a method for treating a subject afflicted with a tumor, e.g., derived from a non-small cell lung cancer (NSCLC), comprising administering to the subject a combination of a (a) chemotherapy, (b) an anti-PD-1 antibody or an anti-PD-L1 antibody, and (c) an anti-CTLA-4 antibody, wherein the chemotherapy is administered for a period of time that is less than the standard.

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

Compounds or their pharmaceutically acceptable salts can modulate the G12D mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds disclosed herein or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The invention relates to the field of natural products, in particular to a dimer compound of guaiane type sesquiterpenes and uric acid as well as an extraction and separation method and application of the dimer compound. According to the invention, a new dimer compound of guaiane type sesquiterpene and uric acid is extracted and separated from carpesium abrotanoides in Guizhou, and it is found that the dimer compound has relatively strong anti-tumor activity. The compound has strong inhibitory activity on breast cancer, prostate cancer, nasopharynx cancer, liver cancer, lung cancer, leukemia, pancreatic cancer, glioma, osteosarcoma, skin cancer, cervical cancer, ovarian cancer, kidney cancer and esophageal cancer, and provides an optional scheme for broad-spectrum anti-cancer drugs. Moreover, in human prostate cancer cells PC3, human cervical cancer cells Hela, human liver cancer cells HepG2 and human glioma cells U87 which are resistant to paclitaxel, the compound also shows strong anti-cancer activity, which indicates that the compound has the potential of treating patients resistant to paclitaxel.

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.

Provided herein, in part, is a compound of Formula (I)or a hydrate thereof,essentially free of one or more impurities, compositions thereof, and methods of use thereof.

The disclosure provides a method of treating a human subject afflicted with lung cancer (e.g., non-small cell lung cancer (NSCLC)) with a programmed death-1 (PD-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and a concurrent chemoradiotherapy (CCRT, e.g., a platinum doublet chemotherapy (PDCT) and a radiation therapy) followed by a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte activation gene-3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody). In some aspects, the method comprises a recovery period that begins upon completion of the treatment with the PD-1 pathway inhibitor and the CCRT and ends at the start of the treatment with the combination of the PD-1 pathway inhibitor and the LAG-3 antagonist.

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 discloses a tumor cholesterol metabolism regulation microneedle patch and a preparation method, the microneedle patch comprises a needle tip and a backing which are connected, the needle tip comprises a needle tip body and nanoparticles loaded on the needle tip body, the nanoparticle is a manganese ion-doped organic metal framework, the outer layer of the manganese ion-doped organic metal framework is modified with a targeting agent, cholesterol oxidase and superoxide dismutase are carried on the manganese ion-doped organic metal framework, the targeting agent can target a CD44 receptor, and the organic metal framework can carry drugs. The targeted drug can enter tumor cells in a targeted mode, superoxide dismutase catalyzes superoxide anions overexpressed in the tumor cells to generate H2O2 and O2, O2 needed by catalysis is provided for cholesterol oxidase, cholesterol at the tumor site is consumed by the cholesterol oxidase, accumulation of 7-DHC is reduced, meanwhile H2O2 can be generated, and the cholesterol oxidase can be used for catalyzing the tumor site. H2O2 is catalyzed by manganese ions through a Fenton-like reaction to generate OH to induce tumor cells to generate ferroptosis, so that ferroptosis-immune synergistic treatment is realized.

The invention relates to application of a targeted inhibition circPDK1 reagent in preparation of an anti-esophageal cancer drug, and belongs to the field of biological medicines. The reagent for targeted inhibition of circPDK1 expression provided by the invention is shRNA or siRNA, and in-vivo and in-vitro experiments prove that the reagent can significantly inhibit circPDK1 expression and inhibit growth and migration of esophageal cancer tumor cells; after siRNA of targeted annular circPDK1 is packaged into efficient and low-toxicity LNP-siRNA, circPDK1 expression is specifically silenced, proliferation and migration of esophageal cancer tumors can be remarkably inhibited, and a basis is provided for clinical treatment and scientific research of esophageal cancer related circRNA.

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

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.

Provided are crystalline and amorphous forms of (Compound 1), and pharmaceutically acceptable salts and compositions thereof, as well as the use of such for treating conditions associated with the inhibition of KRAS(G12D).

Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I): or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof) that degrades Proto-oncogene VAV 1 protein (VAV1). The chemical entities are useful for treating subjects having a disorder or disease that can be treated by reducing the level of VAV1, such as cancer, inflammatory or autoimmune disorders.

The invention belongs to the cross technical field of nanomedicine, tumor treatment and immunotherapy, and particularly provides tumor mitochondria-targeted copper death selective induction nanoparticles, which are prepared by the following preparation method: S1, specifically coupling TPY and MHI through condensation reaction to obtain MTPY; s2, MTPY and copper ions are subjected to complexation, and an MTPY-Cu complex is obtained; and S3, the MTPY-Cu complex and albumin are subjected to self-assembly, and the MTPY-Cu-coated Alb nanoparticles are formed. The dosage of copper is only 1 / 1000 of that of free Cu < 2 + >, and equivalent immune regulation and killing effects can be achieved; primary tumors and distant tumor focuses can be inhibited, and lung metastasis is reduced; immune memory can be induced, and relapse can be prevented; the traditional Chinese medicine composition is combined with cis-platinum to remarkably enhance the curative effect and reverse the induced immunosuppression; the invention has the advantages of high biological safety and no obvious liver and kidney toxicity or hemolytic reaction.

Disclosed are RAS(ON) multi-selective inhibitor compositions and methods of treating RAS protein-related diseases or disorders using an intermittent dosing regimen. RAS(ON) multi-selective inhibitors having tight binding to cyclophilin A (CypA) result in high exposure levels, prolonged tissue retention, and / or slow clearance rates, thereby increasing the risk of inhibition of wild-type RAS in normal tissues. Accordingly, provided herein are methods for the safe and effective dosing of low KD1 RAS(ON) multi-selective inhibitors using an intermittent dosing regimen. Also provided are methods of selecting or identifying such RAS(ON) multi-selective inhibitors suitable for intermittent administration.

Aspects of the application provide anti-hemojuvelin antibodies and methods of using the same in treating myelofibrosis and / or conditions associated with myelofibrosis.

Disclosed herein are methods and compositions for preventing or reducing adverse events associated with administration of a RAS(ON) inhibitors. Thus, disclosed are compositions and methods for treating or preventing RAS(ON) inhibitor therapy-associated rash or mucositis. The methods involve administering a compound that binds to cyclophilin A (CypA) to compete with a RAS(ON) inhibitor for CypA binding, thereby reducing tri-complex formation in non-tumor tissues. These approaches may improve the tolerability of RAS(ON) inhibitor therapies without compromising efficacy.

The present disclosure relates to compositions and methods for reducing expression of MYC gene in a cell. In some embodiments, an expression repressor comprises a targeting moiety that binds a MYC promoter, anchor sequence, or super-enhancer. In some embodiments, the expression repressor comprises an effector moiety that represses transcription or methylates DNA. Systems comprising two expression repressors are also disclosed. The compositions can be used, for example, to treat cancers such as HCC.

Provided herein are novel compounds, for example, compounds having a Formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof. Also provided herein are methods of preparing the compounds and methods of using the compounds, for example, in inhibiting WRN, and / or in treating various diseases such as cancer.

The invention discloses preparation of a whey protein peptide mixture with immune and muscle-building effects, and relates to the technical field of food processing and bioengineering. The neutral protease is adopted and the pH is adjusted, so that the enzymolysis efficiency is effectively improved, and the enzymolysis time is greatly shortened; meanwhile, the whey protein peptide which is uniform in molecular weight distribution, free of peculiar smell and good in thermal stability is successfully prepared by accurately controlling enzymolysis conditions and combining microbial fermentation. The protein peptide can effectively improve thymus indexes and spleen indexes, enhance the proliferation capacity of splenic lymphocytes and the activity of NK cells, play an excellent immune regulation role and have a remarkable muscle building effect. The preparation process has the advantages of high efficiency, low cost, simplicity, convenience and the like, gives consideration to high quality and high functionality of the product, and has great application value.

The present application discloses substituted polycyclic heterocycles compound of Formula (I), pharmaceutically acceptable salt and / or solvate and pharmaceutical compositions thereof useful in the treatment of proliferative disease or condition characterized by a dysregulation of the RAS-ERK pathway such as neoplasm disease or disorder, inflammatory disease or immune system disorder.

The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

The present disclosure is related to dual payload immunostimulatory antibody drug conjugates comprising at least STING agonist and at least one cytotoxic agent, pharmaceutical compositions thereof, and the use of the dual payload immunostimulatory antibody drug conjugates and compositions thereof for the treatment of diseases and disorders, including proliferative diseases.

To provide a pharmaceutical composition for treating a cancer patient having a tumor having a total passenger gene mutation amount larger than the background mutation amount of the tumor.SOLUTION: A pharmaceutical composition for treating a subject having a tumor with a total passenger gene mutation load that is greater than the background mutation load of the tumor, wherein the background mutation load has been determined based on randomly selected genes of the tumor, comprising antibodies that bind to PD1 as an active ingredient. Antibodies that bind PD1 comprise a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 21 and / or comprise a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 22.SELECTED DRAWING: Figure 1