108 results about "Antigen receptors" patented technology

The present disclosure provides CD19 / CD20-binding domains and chimeric antigen receptors (CARs) based on the same, as well as corresponding nucleic acid molecules, vectors, cells, compositions, methods and uses, e.g., for the prevention and / or treatment of cancer and / or autoimmune disease.

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and / or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

This invention provides a chimeric antigen receptor (CAR) targeting both BCMA and GPRC5D antigens and its uses. The chimeric antigen receptor (CAR) includes an extracellular localization signaling domain, an antigen domain targeting BCMA, an antigen domain targeting GPRC5D, a hinge region, a transmembrane region, a co-stimulatory factor, and an intracellular CD3ξ signaling domain. The antigen domain targeting BCMA includes a heavy chain variable region with an amino acid sequence as shown in SEQ ID NO: 1 and a light chain variable region with an amino acid sequence as shown in SEQ ID NO: 2. The antigen domain targeting GPRC5D includes a light chain variable region with an amino acid sequence as shown in SEQ ID NO: 3 and a heavy chain variable region with an amino acid sequence as shown in SEQ ID NO: 4. The dual chimeric antigen receptor, including an antigen domain targeting BCMA and an antigen domain targeting GPRC5D, can simultaneously recognize two anti-tumor targets, preventing tumor immune escape.

Anti-4-1BB single domain antibodies and polypeptides, e.g., bispecific antibodies and chimeric antigen receptors comprising these single domain antibodies, are provided. These antibodies, including humanized antibodies, exhibit superior activity and are suitable for use in various bispecific antibody formats. Methods of using the antibodies or polypeptides to treat and diagnose diseases, e.g., cancer, are also provided.

Described herein are multicistronic expression systems that encode chimeric proteins, specifically membrane-cleavable chimeric systems and chimeric antigen receptors for administration in combination with the cytokine IL2 for treating a subject having cancer. Also described herein are nucleic acids, cells, and methods directed to the same. Also described herein are methods of stimulating a cell-mediated immune response to a tumor, reducing tumor volume, or providing an anti-tumor immunity in a human subject in need thereof, the methods comprise administering to a subject multiple administrations of an immunoresponsive cell encoding a controlled release cytokine.

Provided herein are methods and uses of combination therapies involving a GPRC5D-targeted cell therapy comprising a chimeric antigen receptor (CAR) containing an extracellular antigen binding domain that binds to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and a combination agent, e.g., a bispecific antibody, for treating a subject having a cancer, such as multiple myeloma, as well as related methods, uses, and articles of manufacture.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from the differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

This invention provides a chimeric antigen receptor comprising an NFIX-encoding gene, a self-cleaving peptide sequence F2A, and a CAR-encoding sequence. The NFIX-encoding gene is located upstream and is linked to the CAR-encoding sequence via the self-cleaving peptide sequence F2A. The sequence of the NFIX-encoding gene is shown in SEQ ID NO. 01, and the sequence of the self-cleaving peptide sequence F2A is shown in SEQ ID NO. 03. This invention also provides a chimeric antigen receptor T cell expressing the aforementioned chimeric antigen receptor. This invention further provides the application of the aforementioned chimeric antigen receptor or the aforementioned chimeric antigen receptor T cell in the preparation of drugs for treating cancer. This invention improves the antitumor therapeutic effect of CAR-T cells by introducing the NFIX expression element into engineered T cells, thereby enhancing their functional stability, proliferative capacity, and cytotoxic activity under continuous antigen stimulation.

The present invention relates to novel Chimeric Antigen Receptor (CAR) constructs, including CAR-T constructs, compositions for use with said constructs, and methods of treating patients with cancer and autoimmune diseases.

The present application provides humanized antibodies and antigen binding fragments thereof that bind to human poliovirus (PVR). The antibodies are useful in the treatment of tumors or cancers. The present application also provides a method of treating a cancer in an individual afflicted with a cancer comprising administering to the individual a therapeutically effective amount of chimeric antigen receptor (CAR) NK or T cells.

An mRNA composition for treating cancer is provided. The mRNA composition for treating cancer includes an mRNA encoding a CD47-targeted chimeric antigen receptor (CAR) and an mRNA encoding interleukin-12 (IL-12).

This invention belongs to the field of biomedical technology, specifically disclosing the application of a CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid in the preparation of a drug for treating tumors. Through analysis of the COSMIC database, epitope prediction, and in vitro and in vivo immunomodulatory activity experiments, this invention identified an HLA-A2-restricted CTL epitope peptide derived from the neoantigen ESR1. This mutant epitope peptide originates from a high-frequency mutation of ESR1 and can effectively stimulate and induce the production of neotope-specific cytotoxic T lymphocytes, specifically distinguishing between wild-type and mutant sequences, and killing tumor cells expressing the mutant epitope, exhibiting good anti-tumor effects. The resulting drug for treating tumors may contain the CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid, or may contain a T-cell receptor, chimeric antigen receptor, or its encoded nucleic acid that specifically recognizes the mutant epitope peptide, demonstrating good therapeutic potential and clinical application prospects.

The present disclosure provides orthogonal chimeric cytokine receptor / orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

The present invention relates to the field of cell therapy. Disclosed are a fibroblast activation protein-targeting CAR T-cell, a preparation method therefor, and an application thereof. A CAR T-cell can be prepared by introducing an FAP-targeting chimeric antigen receptor (CAR) into a T lymphocyte, wherein the CAR in the CAR T-cell comprises a signal peptide, an antigen-binding domain, a hinge region, a transmembrane domain, a co-stimulatory signaling region, and a CD3 signaling domain. The CAR T-cell specifically recognizes the FAP by means of a single-chain variable fragment (scFv), which activates an intracellular signaling pathway, releasing cytokine IFN-γ, and exhibiting a cytotoxic effect on FAP+ cells, thereby achieving specific depletion of FAP+ cells at a lesion site. The CAR-T cell can be used for treating diseases characterized by upregulated FAP expression, such as fibrosis (pulmonary fibrosis, hepatic fibrosis, cardiac fibrosis, renal fibrosis, etc.), arthritis, autoimmune disorders (Crohn's disease, rheumatoid arthritis, etc.), and cardiovascular diseases, and demonstrates tremendous application potential and commercial value.

Provided herein are engineered T-celi receptors (TCRs) having nanomoiar affinity for the immuno-dominant pp65 peptide residing between residues 495-503 (NLV) in complex with HLA-A2*02:01. The TCRs may be membrane-hound TCRs, soluble TCRs, chimeric TCRs, or chimeric antigen receptors. Also provided are methods of using the engineered TCRs to treat diseases, monitor disease progression, monitor vaccine efficacy, and detecting NLV / A2 presentation on the surface of cells.

The present application discloses immune effector cells expressing extracellular PD-L1 binding domain CAR and linking secretory interferon fusion protein and application methods thereof. The protein construct involved in the immune effector cells includes: (a) a chimeric antigen receptor (CAR) containing a PD-L1 binding domain; and (b) a secretory fusion protein containing IFN. The protein construct stimulates tumor cells to increase the expression amount or frequency of PD-L1, thereby further enhancing the killing ability of PD1-CAR-T cells on target cells and more effectively inhibiting or killing tumor cells.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are genetically edited, for example, using Crispr / Cas, to modulate, reduce or otherwise eliminate expression of one or more endogenous genes. In several embodiments, the edited cells are engineered to express a chimeric antigen receptor targeting a tumor antigen, for example CD19, ligands of the NKG2D receptor, CD70, and / or BCMA, among others. In several embodiments, the editing enhances one or more aspects of the efficacy of the immune cells in cellular immunotherapy including cytotoxicity (e.g., ADCC) and / or persistence.

Provided herein are chimeric antigen receptors, comprising an extracellular domain capable of binding to an antigen, an Fc region, a flexible linker, a transmembrane domain, and may further comprise at least one intracellular domain that is designed to increase the anti-tumor activities of granulocytes, macrophages, and dendritic cells by increasing their phagocytosis and / or proinflammatory cytokines secretion and / or antigen presentation. Provided herein are vectors and nucleic acid molecules encoding any of the chimeric antigen receptors described herein. Provided herein are methods to genetically engineer granulocyte-macrophage progenitors (GMPs) to express the chimeric antigen receptors described herein. The CAR-Fc-GMPs may be induced to differentiate into macrophages or granulocytes. Provided herein are macrophages and granulocytes that express a CAR-Fc prepared by any of the methods described herein. Provided herein is an immunotherapy method for treating a subject having cancer with GMPs or macrophages or granulocytes that express the chimeric antigen receptors described herein.

Expression constructs encoding chimeric antigen receptors and DAP10 recombinant polypeptides, engineered immune cells, and methods of use thereof are provided. Further provided are methods for activation and expansion of cells for therapeutic use, in particular for chimeric antigen receptor-based immune cell immunotherapy.

The present application relates to the technical field of biomedicine, and in particular to a genetically modified immune cell, and construction and use thereof. The genetically modified immune cell expresses a target protein, the target protein comprises a chimeric antigen receptor and a membrane-bound interleukin, the chimeric antigen receptor comprises an antigen-binding domain that specifically binds to GPC3, and the membrane-bound interleukin comprises a membrane-bound IL-7.

This disclosure relates to a method for determining the potency of an effector cell composition, such as a therapeutic cell composition, for use in conjunction with cell therapy, based on cytotoxicity. The cells of the cell composition may express recombinant receptors, such as chimeric receptors, such as chimeric antigen receptors (CARs), or other transgenic receptors such as T cell receptors (TCRs). The method provides a cytotoxicity assay for identifying the potency of the cell composition, including relative potency.

Compositions and methods for specific expression of RNA or protein are provided, such as a Chimeric Antigen Receptor (CAR) or T Cell Receptor (TCR), in T cells, with limited or no expression in non-T cells.

This invention relates to GPRC5D and BCMA-specific chimeric antigen receptors (CARs), specifically providing CARs containing an extracellular antigen-binding domain that binds to a G protein-coupled receptor class C5 group D member (GPRC5D) and B cell maturation antigen (BCMA). The invention also relates to genetically engineered cells expressing such CARs and their use in adoptive cell therapy.

Therapeutic constructs with surface antigen-regulated (SAP) promoters containing antigen-binding domains are described. Nucleic acids, recombinant expression vectors, host cells, antigen-binding fragments, and related pharmaceutical compositions are also described. Furthermore, methods for treating or preventing cancer in a subject and methods for generating these therapeutic constructs in T cells are described.

The present application relates to a kind of humanized BCMA antibody and its application.The present application designs whole humanization antibody to BCMA target point, the antibody can be highly specific binding human source BCMA protein, based on this antibody constructs chimeric antigen receptor, prepares CAR-T cell, and experiment proves that, CAR-T cell can be efficiently recognized and kill BCMA positive tumor cell in in vitro and in vivo model, significantly inhibit tumor growth proliferation.In tumor-bearing mouse model, the survival time of treatment group mice is significantly prolonged, indicating that the antibody and the CAR therapy derived from the application have clear targeted therapy effect on the related diseases with BCMA as target point.

Embodiments of the disclosure encompass adoptive immunotherapy related to cells expressing multiple chimeric antigen receptors (CARs). In specific embodiments, T cells express a HER2-specific CAR, an IL13Rα2-specific CAR, and an EphA2-specific CAR. In particular embodiments, the cells are utilized for cancer treatment, including for glioblastoma.

The present invention provides a chimeric antigen receptor (CAR) comprising a) an antigen binding domain specific for the antigen CD318 wherein the antigen binding domain comprises SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:9 or SEQ ID NO:11, b) a transmembrane domain, and c) an intracellular signaling domain.

The present invention relates to fibroblast activation protein (FAP)-specific antigen binding molecules, associated fusion proteins and conjugates, and methods of use thereof. In some aspects, the binding molecules comprise a moiety having the form of a shark variable novel antigen receptor (VNAR).

Provided are an anti-CLDN18.2 antibody or an antigen binding fragment thereof, a nucleic acid molecule encoding the antibody, and an immunoconjugate comprising same, a bispecific molecule, a chimeric antigen receptor and a pharmaceutical composition. The antibody or antigen binding fragment thereof is used for preventing and / or treating tumors.