27 results about "Intracellular domain" patented technology

The present invention provides for chimeric antigen receptor constructs capable of being expressed in dendritic cells (DCs), and DCs modified to express one or more chimeric antigen receptors (CARs) as well as compositions comprising these modified DCs and methods of stimulating an adaptive immune response in a subject. The intracellular domain of the CAR comprises a toll-interleukin receptor (TIL) intracellular signalling domain and a costimulating domain selected from CD3 signalling domain, CD28 signalling domain and a combined CD28 and CD3 signalling domain.

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

Provided are a CD19-targeting humanized antibody and chimeric antigen receptor, and the use thereof. The humanized antibody contains CD19 VH and CD19 VL which are selected from one of groups 1) to 8). The CD19-targeting chimeric antigen receptor contains a CD19-targeting extracellular antigen recognition domain, a hinge region, a transmembrane region, and an intracellular domain, wherein the CD19-targeting extracellular antigen recognition domain contains CD19 VH and CD19 VL which are selected from one of groups 1) to 8).

The present invention provides thymic T regulatory cells (ThyTreg cells) that encode or alternatively express a chimeric antigen receptor (CAR) comprising an extracellular domain, a hinge region, a transmembrane domain, and an intracellular domain, wherein the intracellular domain comprises a cytoplasmic costimulatory domain having a sequence having at least 85% identity with SEQ ID NO: 1, and a cytoplasmic stimulatory domain. The present invention also provides compositions and uses in immunotherapy.

Modified natural killer (NK) cells or T cells expressing hematopoietic growth factor receptors are provided. In some aspects, the modified NK cells or T cells express thrombopoietin receptors, erythropoietin receptors, or chimeric peptides comprising an extracellular domain, a transmembrane domain, and an intracellular domain including an intracellular signaling domain of an interleukin receptor. Methods for treating cancer subjects are also provided, comprising administering modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or an erythropoietin receptor agonist, and in some instances, in combination with interleukin-2, particularly reduced or low doses of IL-2.

The invention relates to a chimeric antigen receptor based on a functional fragment of an MAVS protein, in particular to a chimeric antigen receptor (CAR) construct positioned on a cell membrane, and an intracellular structural domain of the CAR construct contains the functional fragment derived from the MAVS protein. The MAVS protein is a truncated body with deletion or mutation of a mitochondrial positioning region of the MAVS protein. The engineered immune cell for expressing the CAR construct disclosed by the invention has specific targeting property and a remarkable anti-tumor effect.

The present application relates to the technical fields of biological medicine and cellular immunotherapy, and particularly relates to a signal conversion receptor targeting IL-10, an engineered macrophage and application thereof. The signal conversion receptor is composed of an extracellular domain and a transmembrane domain and an intracellular domain derived from TLR9, and the extracellular domain sequentially comprises a signal peptide, a HA tag and a specific binding domain of an IL-10 receptor alpha subunit from N-terminal to C-terminal. The present application further prepares an engineered macrophage SR CAR-M capable of specifically recognizing IL-10 and converting it into a TLR9 activation signal, which can induce macrophages to polarize to M1 type and has excellent phagocytosis and killing capacity for bladder cancer, breast cancer, lung cancer and melanoma cells, and can be used for preparing related tumor treatment drugs, overcoming the common problems of existing cell therapy, such as easy exhaustion, difficult infiltration and easy inhibition in solid tumors, and having significant clinical transformation potential.

This invention provides a humanized antibody targeting CD19, a chimeric antigen receptor, and their uses. The humanized antibody comprises CD19VH and CD19VL, selected from groups 1) to 8). The chimeric antigen receptor targeting CD19 of this invention comprises an extracellular antigen recognition domain, a hinge region, a transmembrane region, and an intracellular domain targeting CD19. The extracellular antigen recognition domain targeting CD19 comprises CD19VH and CD19VL, selected from groups 1) to 8).

The present application relates to signal conversion receptors, and specifically provides a signal conversion receptor comprising an extracellular region, a transmembrane region and an intracellular region, wherein the intracellular region comprises a CD25 intracellular domain, and optionally further comprises an intracellular domain of a costimulatory signaling molecule. An immune effector cell expressing the signal conversion receptor has a higher positive rate, activation level and target cell killing ability compared with a control cell.

Provided herein are chimeric antigen receptors, comprising an extracellular domain capable of binding to an antigen, an Fc region, a flexible linker, a transmembrane domain, and may further comprise at least one intracellular domain that is designed to increase the anti-tumor activities of granulocytes, macrophages, and dendritic cells by increasing their phagocytosis and / or proinflammatory cytokines secretion and / or antigen presentation. Provided herein are vectors and nucleic acid molecules encoding any of the chimeric antigen receptors described herein. Provided herein are methods to genetically engineer granulocyte-macrophage progenitors (GMPs) to express the chimeric antigen receptors described herein. The CAR-Fc-GMPs may be induced to differentiate into macrophages or granulocytes. Provided herein are macrophages and granulocytes that express a CAR-Fc prepared by any of the methods described herein. Provided herein is an immunotherapy method for treating a subject having cancer with GMPs or macrophages or granulocytes that express the chimeric antigen receptors described herein.

The application provides a kind of genetic engineering exosome loaded with recombinant XVII type full-length human collagen and preparation and application, it is related to the field of bioengineering technology.The genetic engineering exosome provided by the application retains the intracellular domain, transmembrane domain, extracellular domain of XVII collagen completely, and also increases the exosome sorting signal peptide.The application also provides an extraction and separation method of the genetic engineering exosome loaded with recombinant XVII full-length human collagen and application in burn, scald, alopecia, oral ulcer and skin photoaging.The exosome prepared by the application is highly enriched with recombinant XVII type full-length human collagen on the exosome membrane, and retains the physiological activity of XVII type collagen, promotes the proliferation of epidermal cells, fibroblasts and hair follicle stem cells, plays the role of promoting re-epithelialization, promotes wound healing, promotes hair regeneration and delays skin aging.

This invention discloses an anti-ERBB2 monoclonal antibody, its preparation method, and its applications, belonging to the field of biomedical technology. This anti-ERBB2 monoclonal antibody uses the intracellular domain of the human ERBB2 protein as an immunogen and is obtained through animal immunization, B cell screening, gene cloning, and recombinant expression techniques. It can specifically recognize the human ERBB2 protein, exhibiting high affinity and high specificity, and can recognize both native and denatured ERBB2 proteins. This monoclonal antibody can be applied in immunohistochemistry, immunofluorescence, Western blotting (WB), flow cytometry, ELISA detection, and tumor targeted therapy. Experimental results show that this antibody has low background and no non-specific binding, accurately detecting ERBB2-overexpressing tumor cells and tissues, and has significant application value in the diagnosis, prognostic assessment, and targeted therapy of ERBB2-related diseases such as breast cancer.

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and / or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

The present invention provides compositions and methods for treating T-cell lymphoma and T-cell leukemia. [Solution] A method for treating cancer comprising the steps of administering a first modified cell containing a chimeric antigen receptor (CAR) comprising an antigen-binding domain, a transmembrane domain, and an intracellular domain to the subject, and administering a second modified cell in which the endogenous CD5 gene is knocked out to the subject. Preferably, the antigen-binding domain is an antigen-binding domain that can bind to CD2, CD5, or CD7, and preferably the endogenous CD5 gene is knocked out by the CRISPER / Cas9 method.

The present invention provides a chimeric antigen receptor based on the intracellular domain, comprising sequentially linked extracellular domains, transmembrane domains, and intracellular domains, wherein the extracellular domain comprises an antigen recognition region and a hinge region, and the intracellular domain comprises sequentially linked CD3ε intracellular domain cleavage, a co-stimulatory signaling region, and a CD3ζ intracellular domain. Compared to prior art, the provided chimeric antigen receptor exhibits superior therapeutic effects and fewer side effects, as reflected in improved membrane surface CAR molecule levels of CAR-T cells, better immune synapse formation, superior antigen sensitivity, fewer cytokines, better growth capacity, better sustained proliferation capacity, better repeated killing capacity, reduced NK cell activation and cell depletion, and an increase in stem cell-like and memory cell subsets of CAR-T cells. Furthermore, the chimeric antigen receptor can further enhance the therapeutic effect on tumors and, at the same time, reduce the production of inflammatory cytokines associated with the activation of macrophages and monocytes by downregulating its own cytokines, thereby enabling early prevention of cytokine storms.

Provided herein are proteins, such as chimeric antigen receptors (CARs), such as those specific for BCMA, comprising a CD3-zeta intracellular domain with improved properties. Also contemplated are uses of proteins, such as CARs, comprising a CD3-zeta intracellular domain in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding the same), and methods.

Disclosed are nucleic acids encoding a chimeric antigen receptor comprising an extracellular domain comprising an antigen recognition domain consisting of a fully human single variable heavy (VH) domain that binds a first epitope on B-cell maturation antigen (BCMA), a transmembrane domain, and an intracellular domain comprising a signaling domain.

There is provided a viral glycoprotein comprising a glycoprotein comprising one or more mutations at the intracellular domain of the glycoprotein and / or a modified N-terminal that allows the glycoprotein to be resistant towards detect and / or degradation. The mutations may include lysine to arginine mutations at residues 491, 493, 496, 497 and 511 of the VSV glycoprotein. Also disclosed in a polynucleotide, a vector, a host cell, a composition, a method of treating a disease, and use of the glycoprotein in the manufacture of a medicament for treating a disease.

An object of the present invention is to provide an immune cell capable of favorably surviving and / or proliferating under a cytokine-free culture condition, or in the living body in which a high concentration of cytokine cannot be expected, and a molecule or the like for preparing the immune cell. Membrane-bound IL2, membrane-bound IL7, or membrane-bound IL15, and a TNFRSF molecule-derived intracellular domain are expressed in the immune cell as a combination of different polypeptides, or are both expressed in an immune cell as the single polypeptide.

The present invention belongs to the technical field of biomedicine, and specifically relates to an intracellular signaling domain of a chimeric antigen receptor and the use thereof. The intracellular signaling domain comprises at least two of a1)-a7): a1) FCE or a portion thereof; a2) CD3ζ or a portion thereof; a3) CD40 or a portion thereof; a4) TLR2 or a portion thereof; a5) TLR4 or a portion thereof; a6) IFNgR or a portion thereof; and a7) PI3Krecruit or a portion thereof. The chimeric antigen receptor comprising the intracellular domain can maintain a CAR-positive rate while ensuring the viability and recovery yield of immune cells, thereby better ensuring the activity of CAR-immune cells. Immune cells expressing the chimeric antigen receptor comprising the intracellular domain exhibit significantly enhanced phagocytic, cytotoxic and anti-exhaustion capacities in addition to T cell activation level, thereby achieving more potent antitumor activity and enhanced tumor infiltration.

A chimeric antigen receptor and its uses are disclosed. The chimeric antigen receptor comprises sequentially linked extracellular domains, transmembrane domains, and intracellular domains; the extracellular domain recognizes and binds to an antigen; the intracellular domain comprises an activation domain or a co-stimulatory domain and an activation domain; and, relative to the parent intracellular domain, the lysine of the co-stimulatory domain and / or the activation domain is substituted with glycine. Some of the provided chimeric antigen receptors have an extended half-life and exhibit strong tumor-killing activity even at low effector-to-target cell ratios, which contributes to enhancing the anti-tumor activity of CAR-T against solid tumors and has broad prospects for clinical applications.

The present invention is concerned with a human CD20 protein with modifications to one or more intracellular domains sufficient to reduce or abrogate intracellular signalling when attached to or associated with the membrane of the cell such as (e.g.) a T-cell, a natural killer cell, a B-cell, a myeloid cell, a pluripotent stem cell and a haematopoietic stem cell. The present invention further contemplates a nucleic acid encoding a modified human CD20 protein described herein, and to the utility of the modified human CD20 protein as a safety switch in chimeric antigen receptor T-cell therapy or as a selection marker for gene therapies.

Abstract Modified T cell receptors, cells comprising the modified T cell receptors, nucleic acids encoding the modified T cell receptors, and methods for using the modified T cell receptors are contemplated. Modified T cell receptor comprising two peptide chains are disclosed herein. The two peptide chains may be the same or different, and each peptide chain comprises an extracellular domain comprising a variable region, a constant region, and a connecting peptide, a transmembrane domain, and an intracellular domain comprising a CD28 region and a CD3 ζ ITAM region. Nucleic acids encoding the modified T cell receptors, and vectors comprising the nucleic acids are also disclosed. Additionally, a method for treating cancer and / or a viral infection is disclosed comprising administering a cell comprising the modified T cell receptor. Abstract

Provided are a chimeric antigen receptor (CAR) complex, a CAR-T cell comprising same, a method for preparing same, and use thereof. The CAR complex comprises a CAR and a viral protein. The CAR comprises an extracellular antigen recognition domain, a hinge region, a transmembrane region, and an intracellular domain. The viral protein is selected from at least one of the following proteins: the US2 protein, the US6 protein, the US11 protein, the K3 protein, and the Nef protein. The CAR complex can selectively down-regulate HLA-I molecules on the surface of T cells, such as HLA-A, HLA-B, and HLA-C, thereby reducing the rejection against allogeneic CAR-T cells by T cells of the host without affecting the expression of HLA-E molecules, reducing the rejection against the allogeneic CAR-T cells by NK cells of the host, and improving the persistence of the allogeneic CAR-T cells in the host.

This invention relates to a chimeric antigen receptor complex, CAR-T cells comprising the same, a preparation method therein, and its uses. The chimeric antigen receptor complex comprises a chimeric antigen receptor and a viral protein. The chimeric antigen receptor comprises an extracellular antigen recognition domain, a hinge region, a transmembrane region, and an intracellular domain. The viral protein is selected from at least one of the following proteins: US2 protein, US6 protein, US11 protein, K3 protein, and Nef protein. The chimeric antigen receptor complex of this invention can selectively downregulate HLA-I molecules on the surface of T cells, such as HLA-A, HLA-B, and HLA-C, reducing the host's T cell rejection of allogeneic CAR-T cells, while not affecting HLA-E molecule expression, thus reducing the host's NK cell rejection of allogeneic CAR-T cells and improving the persistence of allogeneic CAR-T cells in the host.