1047 results about "Antigen receptors" patented technology

The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

The present invention is directed to universal T cells and their use in treating diseases and other physiological conditions. More specifically, the present invention is directed to universal T cells and their use in treating treating B-lineage acute lymphoblastic leukemia (B-ALL) in particular and malignancy in general. The universal T cells contain (i) nucleic acid encoding a chimeric antigen receptor (CAR) to redirect their antigen specificity and effector function and (ii) nucleic acids encoding shRNA and/or siRNA molecules to down-regulate cell-surface expression of T cell classical HLA class I and/or II genes to avoid recognition by recipient T cells. The universal T cells may also contain a nucleic acid encoding a non-classical HLA gene, such as an HLA E gene to enforce expression of HLA E genes and/or an HLA G gene to enforce expression of HLA G genes, to avoid recognition by recipient NK cells. The universal T cells may further contain a nucleic acid encoding a selection-suicide gene.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

The present invention belongs to the fields of molecular biology and immunology and relates to a chimeric antigen receptor combining EGFR (epidermal growth factor receptor) family proteins and a composition and uses thereof The present invention particularly relates to the chimeric antigen receptor comprising polypeptides efficiently combining the EGFR family proteins and transmembrane domains, wherein the polypeptides efficiently combining EGFR family proteins comprise HERIN. The chimeric antigen receptor can promote the proliferation ability and killing effect of T cell at the premise of maintaining the killing specificity of the T cell.

A method of typing a variable region of a specific variant of an antigen receptor chain is disclosed. The method comprises: (a) exposing a probe set to a sense or antisense strand of a polynucleotide encoding at least a portion of the variable region of the specific variant of the antigen receptor chain, wherein the probe set includes a plurality of probe molecules, wherein each probe molecule of the plurality of probe molecules is substantially complementary to a sense or antisense strand of a nucleic acid sequence region of a specific polynucleotide encoding a variant of the antigen receptor chain, the nucleic acid sequence region encoding a specific combination of at least two variable region segments of the antigen receptor chain; and (b) measuring a hybridization of each probe molecule of the plurality of probe molecules with the sense or antisense strand of the nucleic acid sequence region of the polynucleotide encoding at least a portion of the variable region of the specific variant of the antigen receptor chain, thereby typing the variable region of the specific variant of the antigen receptor chain.

The invention discloses a CAR-T transgene vector based on replication defective recombinant lentivirus. The CAR-T transgene vector comprises an original nuclear replicon pUCOri sequence, a resistance gene AmpR sequence containing ampicillin, a virus replicon SV40 Ori sequence, a lentivirus packaging cis element, ZsGreen1 green fluorescent protein, an IRES ribosome binding sequence, a human EF1 alpha promoter , a chimeric antigen receptor of second-generation CAR or third-generation CAR and a regulating element, wherein the original nuclear replicon pUCOri sequence is used for plasmid replication; the resistance gene AmpR sequence is used for massively proliferating target strains; the virus replicon SV40 Ori sequence is used for enhancing replication in eukaryocyte; the lentivirus packaging cis element is used for lentivirus packaging; the ZsGreen1 green fluorescent protein is used for expressing green fluorescent for eukaryocyte; the IRES ribosome binding sequence is used for jointly transcribing and expressing protein; the human EF1 alpha promoter is used for conducting eukaryotic transcription on antigen receptor genes; the chimeric antigen receptor is used for forming the second-generation CAR or the third-generation CAR integrating recognition, transfer and start; the regulating element is used for enhancing expression efficiency of transgenes and used after eWPRE-enhanced type woodchuck hepatitis b virus is transcribed. Besides, the invention further discloses a construction method and application of the vector. By means of the CAR-T transgene vector and the construction method and application of the vector, secretion of cell factors and an in vitro killing effect of CAR-T cells can be remarkably improved, and the clinical treatment effect is remarkable.

The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.

The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.

The invention relates to chimeric antigen receptors (CAR), particularly relates to dual-signal independent chimeric antigen receptors (dsCAR), and also relates to immune response cells of the dual-signal independent chimeric antigen receptors (dsCAR) and uses of the immune response cells in preparation of drugs for treatment of malignant tumor and virus infected diseases. In detail, the dual-signal independent chimeric antigen receptors (dsCAR) can respectively identify two different family antigens of tumor cells and can respectively transmit two T-cell-activation related signals. One of the CAR can transmit a first T-cell-activation related signal by combing a ligand of a tumor specific antigen or a tumor-associated antigen to decide T-cell killing specificity, and the other CAR can transmit a second T-cell-activation related signal by combing a ligand of a membrane receptor (such as EGFR (epidermal growth factor receptor) family protein) widely expressed by the tumor cells to promote T cell activation, proliferation and survival. The dual-signal independent chimeric antigen receptors (dsCAR) can avoid the potential safety problems on the basis of maintaining curative effects of second generation and third generation CAR.

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a BCMA monoclonal antibody, conferring specific immunity against BCMA positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas, multiple myeloma and leukemia.

The present invention relates to compositions and methods relating to chimeric antigen receptor (CAR) polypeptides and methods relating thereto. In one embodiment, the present invention relates to engineered cells having chimeric antigen receptor polypeptides directed to at least two targets. In another embodiment, the present invention relates to engineered cells having chimeric antigen receptor polypeptides and an enhancer moiety.

Vector compositions comprising a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a chimeric antigen receptor (CAR) are provided.

The present invention discloses a novel chimeric antigen receptor and applications thereof, wherein the novel chimeric antigen receptor comprises a signal peptide, an antigen binding domain, a transmembrane domain and an intracellular signal domain, and comprises a 4-1BB signal peptide and/or a 4-1BB molecular transmembrane domain. According to the present invention, a variety of chimeric antigenreceptor nucleic acid sequences are separated and purified, the chimeric antigen receptor specifically for CD19 malignant tumor antigens and the CAR-T cells are provided, and the blood cell line malignant tumor killing test results show that the tumor-cell-targeting ability of immune cells is significantly enhanced, and the tumor cell killing activity is enhanced.

The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target cells, such as tumor cells, that have been marked by tagged antibodies. As an example, αFITC-CAR-expressing T cells have been developed that specifically recognize various human cancer cells when those cells are bound by cancer-reactive FITC-labeled antibodies. The activation of αFITC-CAR-expressing T cells is shown to induce efficient target lysis, T cell proliferation, and cytokine/chemokine production. The system can be used to treating subjects having cancer.

The invention relates to a chimeric antigen receptor with stable antigen binding units. The chimeric antigen receptor comprises the extracellular antigen binding units, trans-membrane domains and intracellular co-stimulation signal domains. The antigen binding units can be stably expressed as compared with specific tumor targets and comprise heavy chains and light chains which are connected with one another by hinges of SEQ ID NO.2 (sequence identity number.2) amino acid sequence codes. The invention further relates to cells for expressing the receptor and application of the receptor.

Transcutaneous immunization can deliver antigen to the immune system through the stratum corneum without physical or chemical penetration to the dermis layer of the skin. This delivery system induces an antigen-specific immune response without the use of a heterologous adjuvant. Although perforation of intact skin is not required, superficial penetration or micropenetration of the skin can act as an enhancer; similarly, hydration may enhance the immune response. This system can induce antigen-specific immune effectors after epicutaneous application of a formulation containing one or more antigens. The formulation may initiate processes such as antigen uptake, processing, and presentation; Langerhans cell activation, migration from the skin to other immune organs, and differentiation to mature dendritic cells; contacting antigen with lymphocytes bearing cognate antigen receptors on the cell surface and their stimulation; and combinations thereof. Systemic and/or regional immunity may be induced. Immune responses that provide prophylactic and/or therapeutic treatments are preferred. Antigenic activities in the formulation may be found in the same molecule, two or more different molecules dissociated from each other, or multiple molecules in a complex formed by covalent or non-covalent bonds. For antigens which are proteinaceous, they may be provided in the formulation as a polynucleotide for transcutaneous genetic immunization. Besides simple application of a dry or liquid formulation to the skin, patches and other medical devices may be used to deliver antigen for immunization.

The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.

The present invention relates to the use of interleukin-15 (IL-15) as selectable marker for gene transfer, preferably of at least one gene of therapeutic interest, into a mammalian cell or cell line, in particular a human cell or cell line. The present invention furthermore relates to transgenic mammalian cells or cell lines expressing IL-15 as selectable marker and co-expressing at least one protein of interest encoded by at least one gene of interest, which is preferably a protein of therapeutic interest. The present invention is in particular suitable for chimeric antigen receptors (CARs) as the gene or protein of interest and their expression in lymphocytes. The transgenic mammalian cells and cell lines are furthermore suitable for use as a medicament, in particular in the treatment of cancer and in immunotherapy, such as adoptive, target-cell specific immunotherapy.