29 results about "CCR4" patented technology

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 #

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.

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.

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 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.

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.

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).

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 being bound by 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).

The presently disclosed subject matter relates to methods for selectively attracting cells to a target site in a subject, and methods for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof. Specifically, the disclosed subject matter involves administering to the subject a composition comprising a sustained release microparticle comprising a CCL22 polypeptide, and / or cells expressing a CCR4 polypeptide. The present disclosure further relates to sustained release microparticles comprising a CCL22 polypeptide.

The invention provides a compound and a composition for inhibiting C-C chemokine receptor type 4, and a pharmaceutical composition containing the compound and the composition. The invention also provides, for example, methods of treating or preventing a disease, disorder or condition or a symptom thereof, such as a disease, disorder or condition or a symptom thereof mediated by modulation (e.g., inhibition) of CCR4; also provided are combination therapies of a CCR4 antagonist and one or more checkpoint inhibitors in the treatment of cancer.

The invention provides a recombinant protein combined with chemokines CCL22 and / or CCL17 or a derivative thereof, the recombinant protein is a fusion recombinant protein formed by any combination of extracellular segment parts of a CC chemokine receptor 4 (CCR4), and can also be a fusion recombinant protein obtained by any combination of the fusion recombinant protein and a CCR4 N-terminal recombinant protein. The invention also provides the use of the recombinant protein or derivatives thereof in the treatment, inhibition, amelioration or prevention of diseases or conditions associated with CCR4 signaling.

Aspects of the present invention relate to the use of chemokine receptors such as e.g., CCR4 and CCR6, as homing agents. The chemokine receptor(s) is / are expressed by cells containing synthetic chromosomes. The chemokine receptor(s) is / are under controllable expression from a synthetic chromosome and can be used to control an immune response so as to treat or inhibit a disease such as cancer. The control is provided by inducing leukocyte trafficking to sites of disease. If more than one chemokine receptor is expressed, the levels can be individually controlled so that the desired cellular trafficking pattern can be obtained.

This disclosure provides fused bicyclic heterocyclic compounds and their derivatives of Formula (I), which are therapeutically useful as CCR4 modulators. These compounds are useful in the treatment and / or prevention of diseases and / or disorders that respond to modulation of CCR4 activity. The compounds in this disclosure are especially useful for treating cancer and inflammatory diseases and disorders. This disclosure also provides processes for preparing the compounds and pharmaceutical formulations comprising at least one of the compounds in Formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof.

Provided are a bispecific antibody against human HER2 / CCR4 and a use thereof. Provided is a bispecific antibody capable of simultaneously targeting an HER2 target and a CCR4 target. The bispecific antibody comprises a first antigen-binding region, a second antigen-binding region and an Fc domain, wherein the first antigen-binding region has an HER2-binding activity, the second antigen-binding region has a CCR4-binding activity, and the Fc domain is an Fc domain of a trastuzumab monoclonal antibody. The bispecific antibody can bind to HER2 with a high specificity and a high affinity, and bind to CCR4 with a high specificity and a relatively low affinity. The bispecific antibody promotes effector cells to kill tumor cells and Treg cells in the tumor microenvironment, and effectively avoids the depletion of Treg cells in the peripheral blood caused by CCR4 monoclonal antibodies, thereby having a good anti-cancer activity and a higher safety.