54 results about "Intracellular signalling" patented technology

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

Chimeric antigen receptors (CARs) and bicistronic chimeric antigen receptors (BiCisCARs) that target fibroblast growth factor receptor 4 (FGFR4), CD276, or both are disclosed. The CARs and BiCisCARs include a hinge and transmembrane domain from either CD28 or CD8 and a co-stimulatory domain from either CD28 or 4-1BB. The CARs and BiCisCARs can further include amino acid substitutions in one or more immunoreceptor tyrosine-based activation motifs (ITAMs) of a CD3ζ intracellular signaling domain. Cells expressing the CARs or BiCisCARs can be used for the treatment of cancers that express one or both of FGFR4 and CD276.

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.

The present disclosure describes PLPC-DB, an ultrapure phospholipoproteomic composition consisting of essential phospholipids, bioactive proteins, and intercellular regulatory factors, derived from the supernatant of peripheral blood mononuclear cells (PBMCs). This composition achieves a purity level exceeding 99% through a patented purification process that integrates high-speed advanced centrifugation and selective ultrafiltration, ensuring the structural stability and functional integrity of its bioactive components. PLPC-DB is optimized for advanced research and diagnostic applications, providing reproducibility, consistency, and safety across multicenter studies. The essential biomolecular components of PLPC-DB include phosphatidylcholine and phosphatidylserine, which contribute to membrane stability and intracellular signaling, while cell communication peptides enhance intercellular signaling, homeostatic regulation, and biochemical coordination. Structural and regulatory lipids support cell membrane biogenesis and functional stability, whereas adhesion and signaling proteins mediate cell-cell interactions and immune response coordination. Additionally, bioactive regulatory factors modulate immune and inflammatory responses, contributing to tissue regeneration and metabolic homeostasis.

Provided herein are compositions and methods for treating musculoskeletal fibrosis and / or scarring by gene editing elimination of intracellular signaling through specific cell surface receptors. In some aspects, the compositions and methods relate to TGFB1 ligands. In other aspects, the compositions and methods relate to the TGFB1 receptor (TGFBR1 / TGFBR2). In some aspects, the compositions and methods are useful for treating or preventing post-traumatic fibrosis and / or scarring. In some aspects, the compositions and methods are used to treat or prevent postoperative fibrosis and / or scarring. In some aspects, the compositions and methods are used to treat or prevent local nociceptive feelings, inflammation, degeneration, or morphological changes associated with fibrosis and / or scarring. In some aspects, the compositions and methods are useful for treating fibrosis.

The present disclosure provides an anti-claudin-6 antibody (e.g., a VHH domain antibody) and a chimeric antigen receptor (CAR) that binds to claudin-6. The chimeric antigen receptor includes an anti-claudin-6 antibody in an extracellular antigen-binding domain, a transmembrane domain, and an intracellular signaling domain. Immune effector cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

The present invention relates to a chimeric autoantibody receptor (CAAR) capable of targeting immune cells to B cells that produce autoantibodies. The CAAR comprises an autoantigen or a fragment thereof that binds to autoantibodies associated with a neuroautoimmune disease predominantly targeting the central nervous system. The present invention relates to a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid molecule comprising: a sequence encoding an autoantigen or a fragment thereof that binds to autoantibodies associated with a neuroautoimmune disease predominantly targeting the central nervous system; a sequence encoding a transmembrane domain; and a sequence encoding an intracellular signaling domain. In one embodiment, the autoantigen encoded by the nucleic acid sequence comprises or consists of the following: N-methyl-D-aspartic acid receptor (NMDAR) or one or more NMDAR fragments. The present invention further relates to the chimeric autoantibody receptor (CAAR) protein of the present invention, a vector comprising a nucleic acid molecule encoding the chimeric autoantibody receptor (CAAR) of the present invention, a genetically modified immune cell comprising a nucleic acid molecule encoding CAAR, and the use of the immune cell in the treatment or prevention of a neuroautoimmune disease predominantly targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

Chimeric antigen receptors (CARs) and bicistronic chimeric antigen receptors (BiCisCARs) that target fibroblast growth factor receptor 4 (FGFR4), CD276, or both are disclosed. The CARs and BiCisCARs include a hinge and transmembrane domain from either CD28 or CD8 and a co-stimulatory domain from either CD28 or 4-1BB. The CARs and BiCisCARs can further include amino acid substitutions in one or more immunoreceptor tyrosine-based activation motifs (ITAMs) of a CD3ζ intracellular signaling domain. Cells expressing the CARs or BiCisCARs can be used for the treatment of cancers that express one or both of FGFR4 and CD276.

The present application discloses PLPC-DB, an ultrapurified phospholipoproteomic composition derived from the supernatant of peripheral blood mononuclear cells (PBMCs). It comprises essential phospholipids, bioactive proteins, regulatory peptides, and intercellular signaling factors. The composition exceeds 99% purity through a multi-stage purification process combining high-speed centrifugation and selective ultrafiltration (1-50 kDa), followed by lyophilization. This process ensures structural stability for ≥24 months and inter-batch variability <2%. PLPC-DB supports reproducibility and molecular integrity in research and diagnostic settings. Key components include phosphatidylcholine and phosphatidylserine for membrane stabilization and intracellular signaling; structural and regulatory lipids for membrane biogenesis and immune-relevant components involved in antigen presentation, cytokine modulation, and membrane-associated signaling. These may include structurally defined molecules compatible with immunological evaluation in experimental and non-therapeutic settings. The composition is formulated for bioaccessible delivery via sublingual, endonasal, transdermal, and injectable routes, and is intended exclusively for non-therapeutic use in experimental and translational models.

Disclosed are chimeric antigen receptor (CAR) polypeptides comprising a CD229 antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Disclosed are nucleic acid sequences capable of encoding a CAR polypeptide comprising a CD229 antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Also disclosed are vectors and cells comprising one or both of the CAR polypeptides and nucleic acid sequences capable of encoding CAR polypeptides. Also disclosed are methods of treating.

Aspects of the present disclosure include compositions and methods for treating tumors expressing CD70 with engineered γδ T cells. In some embodiments, the γδ-T cells comprise a chimeric antigen receptor (CAR) construct. The CAR construct can include the full-length CD27 receptor domain, a co-stimulatory domain, an intracellular signaling domain, combinations thereof, or all of them. The CAR construct can contain a domain encoding an additional polypeptide that confers advantageous functions to the γδ T cells.

The invention provides a fusion protein, a nucleic acid construct encoding the fusion protein and regulatory T-cells (Treg) expressing the fusion protein for use in the treatment of inflammatory bowel disease, wherein the fusion protein is a chimeric antigen receptor (CAR) having a single chain variable fragment (scFv) domain specific for being activated by the location of inflammatory bowel disease, especially binding to one of meprin 1α (MEP1A) and cadherin 17 (CDH17), a transmembrane domain and at least one intracellular signalling domain. The scFv domains specific for MEP1A or CDH17 have been found to selectively bind to intestine afflicted by inflammatory bowel disease and to activate suppressive activity in Treg expressing the CAR at the location of inflammatory bowel disease. Specifically, the invention provides a CAR for use in the treatment of an immune response, e.g. in the treatment of an autoimmune response, which is directed against MEP1A or directed against CDH17.

Described are chimeric lactate receptors that act a molecular switches. A chimeric lactate receptor comprises a lactate receptor linked to one or more intracellular signaling domains. Also described are nucleic acids encoding the chimeric lactate receptors, T cell expressing the chimeric lactate receptors, and method of using the T cells to treat cancer.

Provided herein are second generation chimeric antigen receptors (CARs), parallel CARs (pCARs), and adaptor CARs comprising intracellular signaling domains modified to achieve optimal signaling. Also provided herein are compositions and methods for increasing the anti-tumor efficacy and restimulation ability of CAR T cells, pCAR T cells, and adaptor CAR T cells.

The present disclosure provides fusion proteins with novel signaling properties. Disclosed embodiments include fusion proteins that comprise an extracellular component that is capable of binding to a TGFβ polypeptide, a transmembrane component, and an intracellular component comprising a cytoplasmic domain from an IL-2Rβ or IL-2Rγ protein. Certain embodiments include a TGFβR intracellular overhang or overhang sequence extending from a TGFβR transmembrane domain, N-terminal to the IL-2R cytoplasmic domain. In response to TGFβ, the fusion proteins can initiate an IL-2 signal in a host cell, promoting, for example, proliferation of the host cells. Recombinant host cells expressing the fusion proteins, and an optional antigen-binding protein such as a TCR or a CAR, are provided. Also provided are polynucleotides encoding the fusion proteins, and vectors that comprise the polynucleotides. Also provided are compositions and methods comprising the same.

Provided are a CAR library used to screen scFvs that can be functional in CAR-T cells, and an scFv manufacturing method in which the CAR library is used. A chimeric antigen receptor (CAR) library of the present invention includes nucleic acids coding for first CARs. Each of the first CARs includes a first antigen-binding domain, a first transmembrane domain, and a first intracellular signaling domain. The first antigen-binding domain includes a first single-chain antibody (scFv) to be screened for the ability to bind to a target antigen. The first scFv includes a first heavy-chain variable region and a first light-chain variable region. The first heavy-chain variable region and the first light-chain variable region meet a predetermined condition.

The present disclosure provides compositions and methods for targeting neoantigens, for example, to treat or prevent cancer. Embodiments disclosed include binding proteins that bind to neoantigen:HLA complexes, such as T cell receptors. The binding proteins further include a fusion protein of a CD95 ectodomain and a CD137 intracellular signaling domain (Fas-41BB), and a construct comprising a CDS coreceptor α or β chain. The disclosed binding proteins are sensitive to antigens and can induce activation of host T cells with low concentrations of peptide antigens. In certain embodiments, the binding proteins of the present disclosure are (i) non-alloreactive, substantially non-alloreactive, and / or have a low risk of alloreactivity against amino acid sequences derived from the human proteome and / or (ii) human HLA alleles. Polynucleotides encoding such binding proteins can be introduced into host cells, such as T cells, and the cells can be used in immunotherapies for treating various cancers.

The present invention provides a T cell which expresses a gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR), wherein the CAR comprises: an antigen binding domain; a transmembrane domain; and a co-stimulatory intracellular signalling domain; wherein the intracellular signalling domain provides a co-stimulatory signal to the T cell following binding of antigen to the antigen binding domain.

To provide an immune cell expressing a chimeric antigen receptor, wherein the immune cell is modified such that the expression and / or function of lymphocyte-specific protein tyrosine kinase is reduced or eliminated.SOLUTION: An immune cell expressing a chimeric antigen receptor is provided, wherein the chimeric antigen receptor comprises an intracellular signaling domain or a fragment thereof that functions in the absence of lymphocyte-specific protein tyrosine kinase, and the immune cell is modified such that the expression and / or function of lymphocyte-specific protein tyrosine kinase is reduced or eliminated.SELECTED DRAWING: None

The invention relates to compositions and methods for cell therapy. Provided are lentiviral vectors comprising, in operable linkage, sequences encoding a Chimeric Antigen Receptor (CAR), a peptide linker, and a tag suitable for detection, selection, or depletion. The CAR comprises an extracellular antigen binding domain, a transmembrane domain, and intracellular signaling domains. The tag, positioned C-terminally or N-terminally to the linker, facilitates detection and / or selection of host cells expressing the CAR. In certain embodiments, the tag comprises a truncated, non-functional cell surface protein (e.g., hEGFRt) usable as a safety switch for in vivo depletion via cognate binding agents (e.g., antibodies). Also provided are genetically engineered host cells (e.g., T cells, NK cells) transduced with said vectors, pharmaceutical compositions comprising such cells, methods for their manufacture, and methods for treating diseases, such as cancer, using said compositions.

The present disclosure describes PLPC-DB, an ultrapure phospholipoproteomic composition consisting of essential phospholipids, bioactive proteins, and intercellular regulatory factors, derived from the supernatant of peripheral blood mononuclear cells (PBMCs). This composition achieves a purity level exceeding 99% through a patented purification process that integrates high-speed advanced centrifugation and selective ultrafiltration, ensuring the structural stability and functional integrity of its bioactive components. PLPC-DB is optimized for advanced research and diagnostic applications, providing reproducibility, consistency, and safety across multicenter studies. The essential biomolecular components of PLPC-DB include phosphatidylcholine and phosphatidylserine, which contribute to membrane stability and intracellular signaling, while cell communication peptides enhance intercellular signaling, homeostatic regulation, and biochemical coordination. Structural and regulatory lipids support cell membrane biogenesis and functional stability, whereas adhesion and signaling proteins mediate cell-cell interactions and immune response coordination. Additionally, bioactive regulatory factors modulate immune and inflammatory responses, contributing to tissue regeneration and metabolic homeostasis.

The present disclosure relates to hIL2 orthogonal ligands (“IL2 orthologs”) that specifically and selectively bind to the extracellular domain (ECD) a transmembrane polypeptide comprising of a modified hCD122 polypeptide. The binding of the hIL2 ortholog to the modified hCD122 polypeptide participates in the transduction pathway of intracellular signaling resulting in a biological activity of the native intracellular signaling patterns associated with hIL2 binding to either the intermediate or high affinity hIL2 receptor but which exhibits selectivity to an engineered cell expressing an hCD122 orthogonal receptor. The hIL2 orthologs of the present invention exhibit significantly reduced binding relative to their binding to the extracellular domain of wild type hCD122, either alone or when hCD122 is present in the form of an endogenous high or intermediate affinity hIL2 receptors.

The present disclosure relates to immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. The present disclosure also relates to uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease.

The present disclosure relates to immunomodulatory fusion proteins comprising an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a regulatory signal in a host cell such as a T cell. The present disclosure also relates to the use of immune cells expressing such immunomodulatory fusion proteins in the treatment of certain diseases, such as cancer or infectious diseases.

Disclosed herein are engineered immune signaling constructs that can comprise, for example, an extracellular region, transmembrane region, and intracellular region. The extracellular region can comprise a common gamma chain-binding domain, such as a tethered cytokine or gamma chain-binding domain thereof (e.g., "tetherkines") or an antigen-binding fragment of an antibody that binds gamma chain (e.g., "gripperkines"). The intracellular region can comprise an intracellular signaling domain of a common gamma chain family cytokine receptor subunit. The constructs can be configured such that the construct binds to common gamma chain and elicits constitutive gamma chain family cytokine receptor signaling in cells that express the engineered immune signaling construct and common gamma chain, for example, facilitating induction IL2R (e.g., IL2Rbg), IL4R, IL7R, IL9R, or IL21R signaling without requiring presence of a soluble ligand, such as a soluble cytokine.

The present disclosure provides a chimeric antigen receptor for degrading inflammatory cytokines and a recombinant immune cell comprising the same, and specifically provides a chimeric antigen receptor comprising: an extracellular domain specifically binding to a soluble factor, preferably an inflammatory cytokine, more preferably a tumor necrosis factor; a transmembrane domain; an intracellular signaling domain. The invention also specifically provides a recombinant immune cell which comprises the chimeric antigen receptor. The chimeric antigen receptor provided by the invention is a CAR molecule capable of effectively recognizing soluble factors (such as tumor necrosis factors, especially TNF-alpha). Immune cells / recombinant immune cells modified by the molecule can endocytose and degrade soluble factors (such as TNF) in vitro and in vivo. Moreover, the targeted recombinant cell subjected to gene modification shows the curative effects of preventing diseases and efficiently treating and curing the diseases for a long time.

The present disclosure includes methods of treating ocular inflammation or inflammatory ocular conditions, such as uveitis. More specifically the present disclosure relates to inhibiting or reducing the release of inflammatory mediators from inflammatory cells by inhibiting the mechanism associated with the release of inflammatory mediators from granules in inflammatory cells. In this regard, the present disclosure includes an intracellular signaling mechanism that illustrates several novel intracellular targets for pharmacological intervention in disorders involving secretion of inflammatory mediators from vesicles in inflammatory cells. Peptide fragments and variants thereof as disclosed in the present disclosure are useful in such methods.

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.

The present invention relates to a method for culturing T cells, the method comprising a step for bringing a composition containing T cells into contact with a stimulant, wherein the stimulant activates (i) one or more intracellular signaling domains of one or more components of a TCR complex and (ii) one or more intracellular signaling domains of one or more co-stimulatory molecules. This method makes it possible to maintain and proliferate T cells in a composition containing the T cells into a cell group suitable for gene transfer.