73results about "CD45" patented technology

The invention provides improved vector composition comprising chimeric antigen receptor for adoptive T cell therapies.

A mammal lacking expression of particular CD45 isoform in certain cells of the immune system is provided. The mammal may optionally contain a transgene encoding the CD45RO isoform. Also provided are methods of using these mammals.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising : (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, and wherein each of the first and second CARs is an activating CAR comprising an activating endodomain.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, wherein the spacer of the first CAR is different to the spacer of the second CAR and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain.

The invention relates to a mammalian cell, particularly a human cell, expressing a first isoform of a surface protein, wherein the first isoform is functionally indistinguishable, but immunologicallydistinguishable from a second isoform, for use in a medical treatment of a patient having cells expressing the second isoform form of the surface protein. The invention further relates to an agent selected from 1) a compound comprising, or consisting of, an antibody or antibody-like molecule and 2) an immune effector cell bearing an antibody-like molecule or an immune effector cell bearing a chimeric antigen receptor, for use in a method of treatment of a medical condition, wherein the agent is specifically reactive to either a first or a second isoform of a surface protein, wherein the firstisoform is functionally indistinguishable, but immunologically distinguishable from the second isoform, and wherein the agent is administered to ablate a cell bearing the isoform that the agent is reactive to.

The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain; (ii) a membrane tethering component (MTC) which comprises a first dimerization domain; and (Hi) a signal-dampening component (SDC) comprising a signal-dampening domain (SDD) and a second dimerization domain which specifically binds the first dimerisation domain of the membrane-tethering component. Dimerisation between the MTC and SDC may be controllable with an agent, meaning that the agent can be used to control CAR-mediated cell signalling.

The invention provides a chimeric antigen receptor (CAR) and a CAR encoding gene. The CAR comprises an extracellular structural domain capable of binding antigens, a transmembrane structural domain and intracellular immune costimulatory molecules, wherein the extracellular structural domain comprises a D2 structural domain of a Slit2 protein. In addition the invention also provides a chimeric antigen receptor expression cell, and the CAR encoding gene is introduced into the cell, so that the CAR is expressed on the surface of the cell. The CAR or the CAR expression cell provided by the invention can be used as cell medicines in the treatment of tumor diseases. The CAR provided by the invention can be used to modify cells, especially T cells, and modified T cells can specifically recognize and kill or wound tumors and have more efficient tumor killing activity.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first costimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The present invention provides compositions and methods for treating or preventing infection by shiga toxin producing bacteria.

The present invention relates to an anti-L1CAM antibody specifically binding to L1CAM antigen or an antigen-binding fragment thereof, a chimeric antigen receptor comprising the same, and uses thereof. The anti-L1CAM antibody or the antigen-binding fragment of the present invention is excellent in specificity and affinity to L1CAM and thus may be used in the treatment and diagnosis of cancers related to high expression of L1CAM and diseases related to inflammatory disorders. In particular, when the chimeric antigen receptor comprising the anti-L1CAM antibody of the present invention is expressed in effector cells such as T lymphocytes, the chimeric antigen receptor may be effectively used as immunotherapy for cancers related to L1CAM and inflammatory disorders.

Chimeric antigen receptors containing ROR1 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions,relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The present disclosure features, at least in part, methods for conserving cell function, e.g., immune cell function, e.g., after one or more cycles of freezing and / or thawing the nucleated cell. In embodiments, the methods comprise contacting an immune cell with a protein nanoparticle comprising an IL-15 complex.

The invention provides a preparation method and application of enhanced Slit2 CAR-T and CAR-NK cells. The enhanced CAR-T cell comprises a T cell of an enhanced CAR embedded antigen receptor, and the enhanced CAR-NK cell comprises a NK cell of an enhanced CAR embedded antigen receptor, wherein the enhanced CAR embedded antigen receptor includes an extracellular structural domain capable of combining with an antigen, a transmembrane structural domain, intracellular immune costimulatory molecules, an entry site IRES of internal ribosome, and HAC-HSA that are connected in sequence, wherein the extracellular structural domain includes a D2 structural domain of Slit2 protein. The enhanced CAR-T cell and CAR-NK cells can close PDL-1 inhibitory signals, improves the killing activity of CAR-immunocyte, and activates tumor-infiltrating immunocyte. The enhanced CAR-immunocyte can be taken as a cell medicine for treating tumor diseases. The transformed immunocyte can specifically recognize and kill tumor and has efficient tumor-killing activity.

The present disclosure features, at least in part, methods for conserving cell function, immune cell function, e.g., after one or more cycles of freezing and / or thawing the nucleated cell. In embodiments, the methods comprise contacting an immune cell with a protein nanoparticle comprising an IL-15 complex.

A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and / or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

A mammal lacking expression of particular CD45 isoform in certain cells of the immune system is provided. The mammal may optionally contain a transgene encoding the CD45RO isoform. Also provided are methods of using these mammals.

Provided herein are recombinant nucleic acids encoding a T cell receptor (TCR) fusion protein (TFP), modified human immune cells expressing the encoded molecules, and methods of their use in the treatment of diseases, including cancer.

A hyperspecific MP system is a system of at least 3 different types of Modified Proteins expressed on / in any cell type and operating together in a treatment, diagnostic, commercial method, or other commercial method(s). Using multiple Modified Proteins can significantly increase the specificity of cancer treatment among many others and decrease side effects of treatments.

The present invention provides a nucleic acid construct comprising the following structure: A-X—B in which A is nucleic acid sequence encoding a first polypeptide which comprises a first signal peptide; B is nucleic acid sequence encoding a second polypeptide which comprises a second signal peptide and X is a nucleic acid sequence which encodes a cleavage site, wherein the first signal peptide or the second signal peptide comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present invention relates to a method of preserving CD62L expression in an isolated regulatory T cell (Treg) population that has been cryopreserved, comprising introducing a polynucleotide encodin

The present invention relates to a method of preserving CD62L expression in a regulatory T cell (Treg) population that has been cryopreserved, comprising introducing a polynucleotide encoding a FOXP3 polypeptide into the Treg population prior to cryopreservation. The present invention also relates to a method of preserving CD62L in a Treg population after cryopreservation, comprising introducing a polynucleotide encoding a FOXP3 polypeptide into the Treg population and cryopreserving said Treg population. Furthermore, the present invention relates to the use of an exogenous polynucleotide encoding FOXP3 for the preservation of CD62L expression in a Treg population after cryopreservation, and to a cryopreserved engineered Treg, pharmaceutical compositions comprising the cryopreserved engineered Treg and to therapeutic uses thereof.

The invention relates to variants of Target Biological Molecules (TBMs), such as proteins, peptides and other amino acid sequences that are modified to include cysteine residues at predetermined positions within the TBM. The position of amino acid residues within the TBM that are modified to be cysteine residues is selected for its proximity to ligand binding sites within the TBM. Once an amino acid residue, or the DNA encoding the residue, is modified to cysteine, the TBM linked to potential binding ligands by forming a covalent bond through the cysteine thiol (—SH) reactive group of the variant.

Various embodiments of the present disclosure provide therapeutic compositions and related methods comprising Tregs and Tcons for improving hematopoietic stem cell transplantation, including methods for enhancing protection from graft-versus-host disease while maintaining an effective immune response, such as a graft-versus-tumor immune response.

A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and / or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70 % memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain; (ii) a membrane tetheringcomponent (MTC) which comprises a first dimerization domain; and (Hi) a signal-dampening component (SDC) comprising a signal-dampening domain (SDD) and a second dimerization domain which specificallybinds the first dimerisation domain of the membrane-tethering component. Dimerisation between the MTC and SDC may be controllable with an agent, meaning that the agent can be used to control CAR-mediated cell signalling.

Various embodiments of the present disclosure provide therapeutic compositions and related methods comprising Tregs and Tcons for improving hematopoietic stem cell transplantation, including methods for enhancing protection from graft-versus-host disease while maintaining an effective immune response, such as a graft-versus-tumor immune response.

The invention provides compositions and methods for treating a refractory, relapsed or resistant cancer or a chronic infectious disease. In particular the present invention relates to a modified immune cell with reduced SUV39H1 activity, for use in the treatment of a patient suffering from a refractory, relapsed or resistant cancer or suffering from a chronic infectious disease, wherein the cell expresses one or more engineered antigen-specific receptors that bind an antigen associated with the cancer or the chronic infectious disease

Chimeric antigen receptors containing ROR1 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.