39 results about "CCR4" patented technology

The invention discloses a chemokine receptor antagonist, a pharmaceutical composition and application. Specifically, the invention discloses a compound as shown in a formula I, a formula II or a formula III or pharmaceutically acceptable salt thereof, or a deuterated substance thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or a prodrug or a metabolite thereof. The compound provided by the invention has better inhibitory activity on CCR4, and can be used for treating or preventing diseases mediated by CCR4. # imgabs0 #

The invention relates to a polycyclic compound, a preparation method thereof and application of the polycyclic compound in medicine. Specifically, the invention relates to a polycyclic compound as shown in a general formula (I), a preparation method of the polycyclic compound, a pharmaceutical composition containing the compound and application of the compound as a therapeutic agent, especially application of the compound as a CCR4 inhibitor and application of the compound in preparation of drugs for treating and / or preventing CCR4-mediated or dependent diseases or symptoms. # imgabs0 #

Disclosed in the present invention are a spiro heterocyclic compound, a preparation method therefor, and an intermediate and use thereof. Specifically provided is a spiro heterocyclic compound represented by formula (IG) or a pharmaceutically acceptable salt thereof; the spiro heterocyclic compound can be used in the preparation of a drug, particularly in the preparation of a drug for preventing and / or treating CCR4 factor-mediated diseases or illnesses. All groups in formula (IG) are as defined in the description.

The present invention includes compounds and compositions, and methods of use thereof for modulating an RNA transcript, or a precursor, isoform, fragment, or mutant thereof by degradation of the RNA transcript via recruitment or binding of one or more decay factors (e.g., an RNA binding protein).

The invention relates to an anti-HER2 / CD16 / CCR4 trispecific antibody and a preparation method and application thereof.The trispecific antibody comprises a first antigen binding structural domain specifically bound with HER2, a second antigen binding structural domain specifically bound with CD16 and a third antigen binding structural domain specifically bound with CCR4, and the trispecific antibody can be bound with human HER2, CD16 and CCR4 at the same time, so that the trispecific antibody can be used for detecting human HER2, CD16 and CCR4. The anti-tumor activity is obviously enhanced. The trispecific antibody can more effectively activate NK cells, enhance ADCC effect, target HER2 positive tumor cells and remove immunosuppressive cells in a tumor microenvironment, and has the advantages of enhancing antitumor activity and overcoming immunosuppression.

The invention relates to the technical field of disease prognosis and molecular biology, in particular to application of immune-related polygenes in prognosis evaluation of diffuse large B-cell lymphoma. The biomarkers are DES, CHIT1, FGF14, CCR4, CTLA4 and VGF (Vertical Growth Factor). According to the method, core genes related to immunity are screened on the basis of diffuse large B cell lymphoma transcriptome data such as GEO and TCGA, and a multi-gene immune model: RS = (-0.0306) * DES + (-0.4683) * CHIT1 + (1.1418) * FGF14 + (0.1132) * CCR4 + (-0.07) * CTLA4 + (-0.3463) * VGF is constructed; according to the immune polygene immune model, diffuse large B-cell lymphoma patients can be divided into high and low RS groups, the survival prognosis of high-RS people is proved to be obviously lower than that of low-RS people, and the survival prognosis can be used as an independent prognosis index.

Disclosed in the present invention are a heterocyclic compound as shown in formula (I) or a stereoisomer, deuterated compound, solvate, pharmaceutically acceptable salt, or co-crystal thereof and a pharmaceutical composition thereof, and a use thereof in the preparation of a drug for treating / preventing CCR4-mediated diseases. Groups in formula (I) are as defined in the description.

Disclosed herein are methods of synthesis of a trans isomeric form of a C—C chemokine receptor type 4 (CCR4) modulator, or a salt or ester thereof that comprise making a trans isomeric compound of formula (III) by reacting a compound of formula (I) with a compound of formula (II) in the presence of a carboxylic acid directed reducing agent, wherein the compound of formula (III) is in a predominantly trans isomerically pure form.

The present disclosure provides fused bicyclic heterocyclyl compounds of Formula (I) and derivatives thereof, which are therapeutically useful as modulators of CCR4. These compounds are useful in the treatment and / or prevention of diseases and / or disorders responsive to modulation of CCR4 activity. The compounds of the present disclosure are particularly useful in the treatment of cancer as well as inflammatory diseases and disorders. The disclosure also provides methods of preparing such compounds, as well as pharmaceutical formulations comprising at least one compound of Formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof.

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4-IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab arm exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer.

The present invention relates to the field of medicine, and provides a compound as shown in formula (I), a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, a preparation method therefor, a pharmaceutical composition thereof, and a use thereof in preparation of a drug for preventing and / or treating CCR4-mediated diseases.

A method of activating an immune response against brain metastasis in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of an inhibitor of an MCP-1 / CCR2 / CCR4 axis, thereby activating the immune response against brain metastasis in the subject.

This invention provides a method for screening peptides that specifically target T cells, comprising providing T cells having a subset selected from CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L) The T cells are labeled with at least one of the following surface antigen markers: CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7. The T cells are then contacted with a peptide display library, and target peptides that specifically bind to the T cells are screened therefrom.

Provided are a class of compounds as shown in formula III or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing same. Further provided are the use of the compounds or pharmaceutically acceptable salt thereof, and the pharmaceutical composition containing same in the preparation of a drug for preventing and / or treating CCR4-mediated diseases, wherein the CCR4-mediated diseases comprise inflammatory diseases, autoimmune diseases or cancers.

Fc-antigen binding constructs having a CCR4 binding domain and two or more Fc domains are described as are methods for using such constructs. Also described are polypeptides making up such constructs. Fc domain monomers that are included in the constructs can include amino acid substitutions that promote homodimerization or heterodimerization.

Crystalline forms of a C-C chemokine receptor type 4 (CCR4) antagonist, oral dosage forms of same and methods of using and preparing same are provided.

The present invention relates to combination therapies of C-C chemokine receptor 4 (CCR4) antagonists and one or more immune checkpoint inhibitors in the treatment of cancer.

The invention relates to a spiroheterocycle-substituted pyrimidine compound as well as a preparation method and application thereof, and particularly provides a spiroheterocycle-substituted pyrimidine compound as shown in a formula (I) or pharmaceutically acceptable salt thereof, which can be used for preparing medicines, especially medicines for preventing and / or treating CCR4-mediated diseases or symptoms. Each group in the formula (I) is as defined in the specification. # imgabs0 #

The application discloses a vector for editing Nicotiana benthamiana genes based on CRISPR / Cas9 and a construction method and application thereof, and comprises BKG-g10 and / or BKG-g11 vectors constructed for a UbEF1B gene of the Nicotiana benthamiana and / or BKG-g12 and / or BKG-g13 vectors constructed for a CCR4 / NOT gene of the Nicotiana benthamiana. After the UbEF1B gene or the CCR4 / NOT gene is edited by the vectors, the growth state of the Nicotiana benthamiana is normal, and the phenotype does not obviously change compared with a wild type; the vectors do not affect the traits of the Nicotiana benthamiana, and are beneficial to the continuation of offspring. Compared with a traditional breeding method, the CRISPR / Cas9 system can more quickly and effectively obtain disease-resistant materials by editing endogenous genes of the Nicotiana benthamiana.

The invention relates to an anti-HER2 / CCR4 bispecific antibody and an application thereof, and provides a bispecific antibody which can target an HER2 target spot and a CCR4 target spot at the same time, the bispecific antibody comprises a first antigen binding region, a second antigen binding region and an Fc structural domain, the first antigen binding region has HER2 binding activity, the second antigen binding region has CCR4 binding activity, and the Fc structural domain has Fc binding activity. And the Fc structural domain is an Fc structural domain of a Trastuzumab monoclonal antibody. The bispecific antibody can be combined with HER2 with high specificity and high affinity and can be combined with CCR4 with high specificity and relatively low affinity; effect cells are promoted to kill tumor cells and Treg cells in a tumor microenvironment, exhaustion of peripheral blood Treg cells caused by a CCR4 monoclonal antibody is effectively avoided, and good anti-cancer activity and higher safety are achieved.

IL2-CCR4 bispecific immunotoxin, CCR4-IL2 bispecific immunotoxin, and methods of use thereof for treatment of refractory and recurrent human CD25.sup.+ and / or CCR4.sup.+ cutaneous T cell lymphoma, and other human CD25.sup.+ or CCR4.sup.+ tumors. The bispecific immunotoxin can be also used for broad cancer treatment via depleting CD25.sup.+ or CCR4.sup.+ Tregs.

IL2-CCR4 bispecific immunotoxin, CCR4-IL2 bispecific immunotoxin, and methods of use thereof for treatment of refractory and recurrent human CD25+ and / or CCR4+ cutaneous T cell lymphoma, and other human CD25+ or CCR4+ tumors. The bispecific immunotoxin can be also used for broad cancer treatment via depleting CD25+ or CCR4+ Tregs.

Disclosed in the present invention are a heterocyclic compound as shown in formula (I) or a stereoisomer, deuterated compound, solvate, pharmaceutically acceptable salt, or co-crystal thereof and a pharmaceutical composition thereof, and a use thereof in the preparation of a drug for treating / preventing CCR4-mediated diseases. Groups in formula (I) are as defined in the description.

The invention relates to therapies comprising the combination of GM-CSF and the inhibition of CCL22-CCR4 signaling for use in enhancing immune response, e.g. for the treatment of immunogenic cancers. Accordingly, the invention provides methods comprising the administration of GM-CSF and the inhibition of CCL22-CCR4 signaling (e.g. by administration of a CCL22 inhibitor and / or a CCR4 inhibitor) (and the use of the therapeutics) for the treatment or amelioration of one or more symptoms of cancer in a subject in need thereof. The combination therapies provided herein may be combined with other anti-cancer therapies such as immunotherapy and / or treatments reliant on activation / elicitation of the immune response, e.g. vaccination therapies.

Chimeric antigen receptors for use in treating lymphoma-associated C-C chemokine receptor type 4 (CCR4) and other cancers expressing CCR4 are described.

The present invention provides humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from CCR4− IgG1 and recognizes the same epitope. This antibody contains either an IgG4 or a stabilized IgG4 in order to improve binding efficiency and reduce in vivo Fab aim exchange. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of a cancer.

The present disclosure relates generally to compositions and methods for improving the safety of adoptive immune cell therapy, including the use of a depletion tag (e.g., an epitope or a mimotope) that is capable of binding to another molecule (e.g., an antibody) to facilitate the depletion of the engineered immune cells. One class of depletion tags disclosed herein contain an epitope or mimotope derived from a biomarker of a hematologic cancer (e.g., CCR4). A second class of depletion tags disclosed herein contain an epitope or mimotope derived from the same antigen that the engineered receptor binds to (e.g., a DLL3 derived depletion tag for engineered immune cells that bind to DLL3).