33 results about "Single-chain variable fragment" patented technology

The present invention is directed to a monoclonal anti-human CS1 clone 7A8D5 antibody or a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 4 and VL having the amino acid of SEQ ID NO: 5. The present invention is also directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) CS1 scFv of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 4 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

Modified single chain variable fragments (scFv) that specifically bind CD147 are provided. Also provided are chimeric antigen receptors (CARs) including the modified CD147 scFv, nucleic acids encoding the CARs, vectors including the nucleic acids encoding the CARs, and immune cells expressing the CARs. Methods of treating a subject with cancer including administering to the subject an immune cell expressing a disclosed CD147-CAR are also provided.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising VH having the amino acid sequence of SEQ ID NO: 4 and VL having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. A preferred co-stimulatory domain is CD28 or 41-BB. The humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

The present invention relates to: an antibody targeting a mutation of KRAS as an intracellular oncoprotein; or a fusion protein in which a cancer cell-penetrating peptide is linked to a single-chain variable fragment of the antibody by a genetic expression method or a chemical bonding method; and a tumor therapeutic use thereof. The fusion protein thus produced has the benefit of maximizing an anti-tumor or anticancer effect of the antibody or the single-chain variable fragment of the antibody targeting an intracellular oncoprotein or an oncomutant protein by effectively invading tumor cells.

The present invention relates to a mutant protein of a single-chain variable fragment having improved stability and, more specifically, to a mutant protein of a single-chain variable fragment having excellent binding affinity to immune checkpoint molecules and superior in vivo stability, in which a heavy-chain variable region including CDRH1 of SEQ ID NO: 1, CDRH2 of SEQ ID NO: 2, and CDRH3 of SEQ ID NO: 3 and a light-chain variable region including CDRL1 of SEQ ID NO: 4, CDRL2 of SEQ ID NO: 5, and CDRL3 of SEQ ID NO: 6 are linked by a stability-enhancing linker of SEQ ID NO: 7.

The present disclosure provides compositions and uses for binding a chimeric antigen receptor (CAR) or an antibody or antigen-binding fragment to the Vβ region of a T cell receptor. It also provides a method for treating diseases such as cancer or an autoimmune disease using a Vβ region-targeting molecule. The present disclosure provides a chimeric antigen receptor (CAR) comprising: (i) an antigen-binding molecule that specifically binds to a TCR Vβ region; (ii) an extracellular domain; (iii) a transmembrane domain; (iv) a costimulatory domain; and (v) an activation domain, wherein the antigen-binding molecule is a single-chain variable fragment (scFv) comprising a variable heavy chain (VH) set forth in any one of SEQ ID NOs: 45 to 131 and 534 to 544 and / or a variable light chain (VL) set forth in any one of SEQ ID NOs: 132 to 227 and 545 to 558.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and / or formulation thereof comprising the alpha and beta multi-subunits cytokines, such as IL-12 or IL-27, fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

The present invention belongs to the technical fields of biomedicine and molecular biology, and particularly relates to a single-chain fragment variable (scFv) targeting human platelet-derived growth factor receptor (PDGFR)-β and use thereof in chimeric antigen receptor (CAR)-T cell immunotherapy. In the present invention, a scFv sequence targeting a human-derived PDGFRβ antigen is first obtained by immunizing a mouse, and then a second-generation CAR is constructed based on this, and additionally a CAR-T cell is obtained via lentivirus infection. The CAR-T cell can effectively kill a PDGFRβ antigen-positive 293T cell. The present invention provides a brand-new idea for eliminating PDGFRβ-positive cells to treat chronic kidney diseases, chronic liver diseases, cardiovascular diseases and various tumor diseases including various organ fibrosis, and has extremely attractive further development value and application prospects.

The present disclosure relates to novel nucleic acids for immune cell adapters, comprising a ribonucleic acid of formula I: R1-SP-R2-R3-R4-R5 (I) wherein R1 is a 5'non-transcriptional region (UTR); sP encodes a signal peptide; r2 encodes a first single chain variable fragment (scFv) that binds to a first extracellular protein or a heavy chain variable region (VH only) that binds to a first extracellular protein; r3 encodes a second scFv that binds to a second extracellular protein; r4 encodes a half-life extender; r < 5 > is 3 'UTR wherein R < 1 > to R < 5 > are in the 5' to 3 'direction for use in the treatment of cancer, including but not limited to hematological cancers, including multiple myeloma.

The present disclosure provides compositions and methods related to the purification and / or isolation of antibodies. In particular, the present disclosure provides novel peptide ligands capable of targeting the fragment antigen binding (Fab) domain and / or single-chain variable fragment (scFv) of antibodies to facilitate the isolation and / or purification of antibodies from processing fluid streams. The novel ligands disclosed herein are capable of universal and subtype-specific biorecognition.

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 are anti- DLL3 chimeric antigens receptors (CARs), DLL3 binding proteins, and uses of such CARs or DLL3 binding proteins in the treatment of DLL3 associated disorders (e.g., small cell lung carcinoma).SOLUTION: Provided is a chimeric antigen receptor (CAR) comprising a DLL3 binding domain, wherein the DLL3 binding domain comprises or is derived from a single domain antibody (sdAb) or a single chain variable fragment (scFv).SELECTED DRAWING: None

This document provides methods and materials for assessing a mammal having or suspected of having cancer and / or for treating a mammal having cancer. For example, molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen), as well as method for using such molecules, are provided.

The present disclosure provides a method of treating autoimmune diseases such as multiple sclerosis, comprising the use of anti-CD20 chimeric antigen receptor (CAR) that contains a hybrid single chain variable fragment (scFv), wherein the framework regions (FRs) and complementarity-determining regions (CDRs) of the scFv are derived from different anti-CD20 antigen binding regions or anti-CD20 antibodies. Furthermore, the CAR comprises a torsional linker (e.g. 1-4 alanine residues) between the transmembrane domain and the cytoplasmic region of the CAR.

The present invention relates to a monoclonal mouse or humanized ROR1 antibody or single chain variable fragment (scFv). The present invention also relates to a mouse or humanized ROR1 chimeric antigen receptor (CAR) comprising from N-terminus to C-terminus: (i) a single chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one costimulatory domain, and (iv) an activating domain.

The present invention relates to an antibody drug conjugate using a bispecific antibody and use thereof. According to the antibody drug conjugate of the present invention, by binding a conjugate of a bivalent calicheamicin peptide and a drug to an anti-calicheamicin single chain variable fragment, a complex of an antibody and a drug can be easily formed without a multi-step synthetic process. In addition, the antibody drug conjugate of the present invention can effectively deliver a drug to a target to which an antibody specifically binds, and can enhance a therapeutic effect by increasing a half-life of a drug in vivo.

The present application relates to ligands targeted to epidermal growth factor receptor (EGFR) and compositions for use in treating tumors. Specifically, a ligand targeted to EGFR is disclosed. The ligand comprises a heavy chain variable domain and a light chain variable domain. The ligand may be selected from the group consisting of a single chain variable fragment, a fusion protein, a monoclonal antibody, and an antigen-binding fragment thereof. The ligand may be conjugated to a liposome or a nanoparticle that encapsulates at least one chemotherapeutic agent to form a ligand-targeted liposomal or nanoparticle drug. Also disclosed are conjugates and formulations for use in treating tumors such as squamous cell carcinoma of head and neck. A method for making a ligand-targeted liposomal drug is also disclosed. The drug may be a chemotherapeutic agent selected from the group consisting of doxorubicine and vinorelbine.

Disclosed are antigen binding molecules that specifically bind to the TROP2 extracellular domain. The antigen binding molecules include a single-chain variable fragment (scFv) and an antibody comprising a VH having a specific amino acid sequence and VL having a specific amino acid sequence. Diagnostic and therapeutic methods of using the same are also disclosed.

The present technology relates generally to carbon nanotube antibody fragment conjugates useful for the detection of a bioanalyte, and methods of making and using the same. In particular, a conjugate for detection of a bioanalyte includes a single-walled carbon nanotube with a sp3 quantum-well defect site (QWNT) conjugated to an antibody fragment via an amide bond at the sp3 quantum-well defect site; wherein the antibody fragment is a single-chain variable fragment with an overall net charge of about -10 to about -30 at a pH of about 6.5 to about 7.5, the antibody fragment changes phase in response to interaction with the bioanalyte, and the antibody fragment comprises Vu-linker-Vr, wherein VH is a variable heavy chain domain, Vi. is a variable light chain domain; and wherein the antibody fragment comprises a number of D residues to provide the overall net charge.

Disclosed are a single-chain fragment variable (scFv) targeting KRAS G12V, a chimeric antigen receptor (CAR), and a use thereof. Based on the KRAS G12V target, a T cell receptor (TCR) is modified. An extracellular signaling domain of the TCR for recognizing a tumor-specific antigen (TSA) is retained and linked in series to an extracellular spacer, a transmembrane domain, and a CD3ζ-derived intracellular signaling domain in the conventional CAR structure, such that the modified CAR can specifically recognize a KRAS G12V mutant polypeptide presented by HLA-A*02:01. Moreover, based on the advantages of CAR-T cell / NK cell therapy, potential new tumor treatment options are explored to lay a foundation for clinical trials.

The invention belongs to the technical field of biological medicine, and discloses a CCR9-targeted chimeric antigen receptor and application thereof, the chimeric antigen receptor comprises an antigen binding structural domain, a hinge region, a transmembrane structural domain, a co-stimulation structural domain and a signal transduction structural domain which are connected in sequence from N terminal to C terminal; wherein the C end of the signal transduction structural domain is further connected with a CXCR4 chemotactic factor receptor structural domain, and the amino acid sequence of the CXCR4 chemotactic factor receptor structural domain is as shown in SEQ ID NO. 2; the antigen binding structural domain is an anti-CCR9 single-chain variable fragment, and the amino acid sequence of the anti-CCR9 single-chain variable fragment is as shown in SEQ ID NO. 1. The CAR enables immune cells expressing the CAR to obtain stronger tissue chemotactic ability and in-vivo distribution breadth through the energization of CXCR4, and particularly, the ability of the CAR to migrate to bone marrow is remarkably improved, so that the CAR is more beneficial to treatment of acute T lymphocytic leukemia.

The present disclosure relates to chimeric antigen receptor (CAR) comprising an extracellular antigen binding domain comprising a modified single chain variable fragment (scFv) that specifically recognises lambda myeloma antigen (LMA). The present disclosure also relates to a polynucleotide encoding the CAR, vectors, genetically modified cells and uses thereof.

Antibodies can treat neurodegenerative disorders (NDs) caused by misfolded proteins. Still, the blood-brain-barrier (BBB) resists their entry, a barrier that can be reduced by scFv instead of whole antibody and conjugating it with transferrin protein to induce transcytosis. While the scFv binds variable heavy and light chains with a non-cleavable linker, a cleavable linker between the scFv and transferrin protein can reduce exocytosis, enhancing the activity of the scFv.

The present technology relates generally to carbon nanotube antibody fragment conjugates useful for the detection of a bioanalyte, and methods of making and using the same. In particular, a conjugate for detection of a bioanalyte includes a single-walled carbon nanotube with a sp3 quantum-well defect site (QWNT) conjugated to an antibody fragment via an amide bond at the sp3 quantum-well defect site; wherein the antibody fragment is a single-chain variable fragment with an overall net charge of about -10 to about -30 at a pH of about 6.5 to about 7.5, the antibody fragment changes phase in response to interaction with the bioanalyte, and the antibody fragment comprises Vu-linker-Vr, wherein VH is a variable heavy chain domain, Vi. is a variable light chain domain; and wherein the antibody fragment comprises a number of D residues to provide the overall net charge.

Antibodies can treat neurodegenerative disorders (NDs) caused by misfolded proteins. Still, the blood-brain-barrier (BBB) resists their entry, a barrier that can be reduced by scFv instead of whole antibody and conjugating it with transferrin protein to induce transcytosis. While the scFv binds variable heavy and light chains with a non-cleavable linker, a cleavable linker between the scFv and transferrin protein can reduce exocytosis, enhancing the activity of the scFv.

Antibodies can treat neurodegenerative disorders (NDs) caused by misfolded proteins. Still, the blood-brain-barrier (BBB) resists their entry, a barrier that can be reduced by scFv instead of whole antibody and conjugating it with transferrin protein to induce transcytosis. While the scFv binds variable heavy and light chains with a non-cleavable linker, a cleavable linker between the scFv and transferrin protein can reduce exocytosis, enhancing the activity of the scFv.

MUC1 is overexpressed in many cancers, including those of the lung, colon, breast, ovary, and pancreas. Aspects of the invention are directed towards the discovery of monoclonal antibodies and fragments thereof, such as a human single chain variable fragment (scFv), that recognizes human MUC1-SEA.

Disclosed are compositions and methods for targeted treatment of TAG-72-expressing cancers. In particular, affinity maturated single chain variable fragment (scFv) antibodies that bind TAG-72 on cancer cells are disclosed.

The present disclosure relates to an anti-glucose-related protein 78 (GRP78) antibody or an antigen-binding fragment thereof. The anti-GRP78 antibody or antigen-binding fragment thereof, such as a single chain variable fragment, can be used as an antigen binding domain of chimeric antigen receptors (CARs) or immunoconjugates for treating and / or preventing a disease and / or disorder caused by or related to GRP78 activity or signaling. The present disclosure also relates to a method or kit for detecting GRP78 or a cancer in a sample.