35 results about "Intracellular signalling" patented technology

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.

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.

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.

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.

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 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 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.

Compositions and methods for the treatment of neurodegenerative diseases are provided. Aspects of the present disclosure provide for a chimeric antigen receptor (CAR) constructs including: an antigen-binding domain; a hinge; a linker; a transmembrane protein (e.g., CD28, CD8); and a phagocytosis-inducing intracellular signaling domain. In some embodiments, the CAR includes a Dectin1 sequence. In some embodiments, the CAR construct includes a Megf10 sequence.

The present invention relates to an isolated chimeric antigen receptor (CAR) molecule comprising an antibody or an antibody fragment comprising an anti-CD123 binding domain, a transmembrane domain and an intracellular signaling domain comprising at least a stimulating domain, and wherein the anti-CD123 binding domain comprises a heavy chain comprising a complementarity determining region 1 (CDR1) having at least 90% identity to the amino acid sequence SEQ ID NO: 1, a complementarity determining region 2 (CDR2) having at least 90% identity to the amino acid sequence SEQ ID NO: 2, and a complementarity determining region 3 (CDR3) having at least 90% identity to the amino acid sequence SEQ ID NO: 3, and a light chain, the light chain comprises a complementarity determining region 1 (CDR1) having at least 90% identity with the amino acid sequence SEQ ID NO: 4, a complementarity determining region 2 (CDR2) having at least 90% identity with the amino acid sequence serine-threonine-serine (STS), and a complementarity determining region 3 (CDR3) having at least 90% identity with the amino acid sequence SEQ ID NO: 5, the separated chimeric antigen receptor molecule is used for treating autoimmune diseases.

Provided in the present disclosure are a chimeric antigen receptor for degrading an inflammatory cytokine, and a recombinant immune cell containing same. Specifically, provided is a chimeric antigen receptor, comprising: an extracellular domain, wherein the extracellular domain specifically binds to a soluble factor, preferably an inflammatory cytokine, and more preferably a tumor necrosis factor; a transmembrane domain; and an intracellular signaling domain. Specifically, further provided in the present disclosure is a recombinant immune cell containing the chimeric antigen receptor. The chimeric antigen receptor provided in the present disclosure is a CAR molecule capable of effectively recognizing a soluble factor (such as a tumor necrosis factor, especially TNF-α). The immune cell / recombinant immune cell modified by the molecule can endocytose and degrade a soluble factor (such as TNF) in vitro and in vivo. Moreover, the genetically-modified targeted recombinant cell demonstrates efficacy in disease prevention, long-term high-efficiency treatment and curing a disease.

The present invention relates to the field of biotechnology, specifically to an isolated alternative intracellular signalling domain of a chimeric antigen receptor (CAR) and to a chimeric antigen receptor (CAR) comprising, said signalling domain. The invention also relates to a nucleic acid coding an alternative intracellular signalling domain of a chimeric antigen receptor, and to a nucleic acid coding a chimeric antigen receptor with the above-mentioned signalling domain, to an expression vector, to a delivery vector, and also a genetically modified cell which comprises the above-mentioned chimeric antigen receptor, and to a method for producing said cell.

Provided herein are cells, methods, kits and articles of manufacture, including those related to assessing the potency of viral vectors. The present disclosure relates to a method for screening for potency of a viral vector, including vectors which encode recombinant receptors that contain an extracellular antigen-binding domain and an intracellular signaling domain, such as a chimeric antigen receptor (CAR). The methods include assessing potency of a viral vector based on a detectable or measurable expression or activity of a reporter molecule(s) that are responsive to a signal through the intracellular signaling region of the T cell receptor e.g., recombinant receptor.

The present invention provides a chimeric antigen receptor (CAR) comprising an extracellular BCMA binding domain, in particular an scFv. The CAR further comprises a spacer having a length of at least 125 amino acids, a transmembrane domain, and an intracellular signaling region. It may also comprise an intracellular co-stimulation domain. Also provided are genetically engineered cells expressing the CARs and their use in, for example, adoptive cell therapy.

The present disclosure provides a chimeric antigen receptor (CAR) directed against human C-type lectin-like molecule-1 (CLL-1) comprising a polypeptide comprising: an extracellular antigen binding domain comprising an anti-CLL-1 single heavy chain variable domain (VH) and an anti-CLL-1 single light chain variable domain (VL); a transmembrane domain; and an intracellular signaling domain. Also disclosed are immune effector cells comprising the CARs and pharmaceutical compositions based on the immune effector cells, as well as their therapeutic uses in the treatment of CLL-1 related conditions.

Provided herein are chimeric antigen receptors (CARs) comprising an extracellular BCMA binding domain, in particular a scFv. The CAR further comprises a spacer of at least 125 amino acids in length, a transmembrane domain, and an intracellular signaling region. It can further comprise an intracellular costimulatory domain. Also provided are genetically engineered cells expressing the CAR and their use in, for example, adoptive cell therapy.

Provided herein are anti-PILRA antibodies with the highly desirable selectivity: having comparable binding to cynomolgus and human PILRA proteins, but much weaker binding to human PILRB protein, as well as binding to both PILRA G78 and R78 variants. The binding and selectivity profiles of the antibodies described herein allow for them to be used in animal studies (e.g., monkeys) without the need to rely on a surrogate molecule and also when treating subjects with either PILRA variant. Further described herein, for the first time, are biological discoveries related to PILRA and the effects of reducing PILRA signaling in cells.

Provided herein are novel synthetic pathway activators comprising transmembrane domains and tiled intracellular signaling domains comprising a combinatorial signaling domain comprising two or more Signal Transducer and Activator of Transcription (STAT)1, STAT3, STAT4, STAT5 and / or Toll-like receptor (TLR) / IL-1R (TIR) signaling domains(s).

The present application relates to a kind of bifunctional CAR-NRR-T cell and its application, the bifunctional CAR-NRR-T cell is obtained by the intracellular signal transduction domain fusion of NRR-scFv and CD19 CAR construction.The present application is verified by experiment, in MEC-1 cell (human CLL cell line) xenograft mouse model, compared with traditional CD19 CAR-T monotherapy, using the present application reinforced combination therapy (NRR-scFv-T cell→bifunctional CAR-NRR-T cell) realizes the fastest, deepest tumor clearance, curative effect is superior to all other treatment groups.

Compositions and methods for treating musculoskeletal fibrosis and / or scarring by eliminating intracellular signaling through specific cell surface receptors via gene editing are provided herein. In some embodiments, the compositions and methods target a TGFB1 ligand. In other embodiments, the compositions and methods target a TGFB1 receptor (TGFBR1 / TGFBR2). In some embodiments, the compositions and methods are for treating or preventing post-traumatic fibrosis and / or scarring. In some embodiments, the compositions and methods are for treating or preventing postoperative fibrosis and / or scarring. In some embodiments, the compositions and methods are for treating or preventing local pain, inflammation, degeneration, or morphological changes associated with fibrosis and / or scarring. In some embodiments, the compositions and methods are for treating fibrosis.

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.

The application discloses a preparation method and application of a LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signaling domain and an intracellular signaling domain, wherein 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, wherein CDR-H1, CDR-H2 and CDR-H3 are respectively composed of the amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, and CDR-L1, CDR-L2 and CDR-L3 are respectively composed of the amino acid sequences of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The invention discloses a yak ear fibroblast immortalized cell line and a construction method thereof, and relates to the technical field of biology. The method comprises two parts of optimization: (1) optimization of a gel recovery process: beta-glucan with the final concentration of 0.2-0.5 mol / mL is added during gel recovery, so that the problems of gene degradation and low recovery rate caused by improper pH value of a gel recovery buffer solution, excessive washing, insufficient elution and the like in the prior art are effectively solved, and the recovery quality and efficiency of a target fragment are remarkably improved; (2) improvement of the cryopreservation liquid: on the basis of a traditional cryopreservation liquid (fetal calf serum: DMSO = 9: 1), a trehalase inhibitor with the final concentration of 0.1-1.0 mol / mL is added, the toxic influence of DMSO on cells is reduced, the leakage of substances in the cells is reduced, the permeability of cell membranes is stabilized, and the normal operation of signal transduction channels in the cells is guaranteed, so that the recovery survival rate of the cells is increased, and the survival rate of the cells is increased; and normal growth, proliferation and differentiation functions of cells are maintained.