23 results about "Intracellular signalling" 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.

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 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 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 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 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.

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.

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.

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.

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 present application provides an anti-human CD153 monoclonal antibody, or a binding fragment thereof, that specifically binds to human CD153 and inhibits the intermolecular interaction between human CD153 and CD30. The present application further provides: a chimeric antigen receptor comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular signal transduction domain wherein the extracellular antigen binding domain comprises a single-chain antibody having a heavy chain hypervariable region and a light chain hypervariable region which are the same as those of the monoclonal antibody of the present application; the invention also discloses a CAR-T cell for expressing the chimeric antigen receptor. The monoclonal antibody, the binding fragment of the monoclonal antibody and the CAR-T cell can be used for treating or preventing diseases related to CD153, such as multiple sclerosis. The invention provides the anti-human CD153 monoclonal antibody or the binding fragment of the anti-human CD153 monoclonal antibody which specifically binds to human CD153 and inhibits intermolecular interaction between the human CD153 and CD30. The present application further provides: a chimeric antigen receptor comprising an extracellular antigen binding domain, a transmembrane domain and an intracellular signal transduction domain wherein the extracellular antigen binding domain comprises a single-chain antibody having a heavy chain hypervariable region and a light chain hypervariable region which are the same as those of the monoclonal antibody of the present application; the invention also discloses a CAR-T cell for expressing the chimeric antigen receptor. The monoclonal antibody, the binding fragment thereof and the CAR-T cell can be used for treating or preventing diseases related to CD153, such as multiple sclerosis.

Provided herein are proteins containing CD3 zeta intracellular domains having improved properties, such as BCMA-specific chimeric antigen receptors (CARs). The use of CD3 zeta intracellular domain-containing proteins such as CARs in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding them), and methods is also intended.

The application discloses a preparation method and application of a CLEC12A-targeted chimeric antigen receptor T cell. The chimeric antigen receptor comprises a CLEC12A antigen binding domain, a transmembrane domain, a costimulatory signaling domain and an intracellular signaling domain, wherein the CLEC12A 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.