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

The invention discloses a CA9-targeted chimeric antigen receptor and application thereof, and belongs to the technical field of biological medicines. The CA9 targeting chimeric antigen receptor provided by the invention comprises a CD8 alpha leading signal peptide, an anti-CA9 single-chain variable fragment, a CD8 alpha hinge, a CD8 transmembrane structural domain and a CD3 zeta intracellular costimulatory signal transduction structural domain. According to the invention, an anti-CA9 single-chain variable fragment is used as an antigen binding structural domain to construct a chimeric antigen receptor (CAR) molecule, the macrophage expressing the anti-CA9CAR can realize specific targeting and phagocytosis killing of CA9 positive kidney cancer cells, and the constructed lipid nanoparticle delivery system can effectively transfer a gene expression vector, so that the gene expression vector can realize effective target site delivery, and the CA9 positive kidney cancer cells can be effectively targeted and killed. The constructed hydrogel-liposome combined drug delivery system has the performance of relieving toxic and side effects, controllable release and hemostasis.

The present invention is directed to a humanized monoclonal anti-human EpCAM antibody, such as a single-chain variable fragment (scFv), comprising VH having the amino acid of SEQ ID NO: 2 and VL having the amino acid of SEQ ID NO: 4. The present invention is also directed to a 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.

The invention relates to the technical field of biology, in particular to a bispecific antibody and application thereof. The invention provides a bispecific antibody which has neutralizing activity on an SARS-CoV-2 mutant strain (VOCs) and an SARS-related coronavirus (SARSr-CoVs), and the bispecific antibody is constructed by fusing single-chain variable fragments of the two antibodies through a GS linker. The bispecific antibody shows high binding capacity to S1, and has broad-spectrum and efficient activity to pseudovirus SARS-CoV-2 variants and SARS-related coronaviruses, so that the bispecific antibody provided by the invention has the potential of preventing and treating the SARS-CoV-2 and the SARS-related coronaviruses.

The disclosure provides for single chain variable fragments to oxidized phospholipid epitopes and methods of use thereof, including the production of transgenic animal models and the use of the fragments as therapeutic agents for treating CAS.

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.

Described herein are receptor configurations that allow ligation of multiple targets expressed in cancer cells via two main mechanisms: direct binding via an antibody-derived single chain variable fragment (scFv), and indirect binding through the high-affinity engagement of the Fc component of an antibody. When expressed in human T lymphocytes, these receptors (CARFcR) can trigger powerful CAR-T cell activity as well as antibody- dependent cell cytotoxicity (ADCC), either simultaneously or sequentially. CARFcR T cells are not affected by soluble antibodies, but they can be redirected and activated by antibodies bound to target cells. Therefore, such T cells can be used to redirect adoptive T cell therapy towards another tumor-associated antigen "on the fly" using clinically available antibodies. They also provide a practical way to target multiple antigens simultaneously with a single receptor, a feature that should be useful in cell therapies directed against phenotypically heterogeneous tumors.

To provide CD147 chimeric antigen receptors and methods of use.SOLUTION: Modified single chain variable fragments (scFv) that specifically bind CD147 are provided. Also provided are chimeric antigen receptors (CARs) comprising the modified CD147 scFv, nucleic acids encoding the CARs, vectors comprising the nucleic acids encoding the CARs, and immune cells expressing the CARs. Also provided is a method of treating a subject having cancer, the method comprising administering to the subject an immune cell expressing the disclosed CD147-CAR. The disclosure relates to immunotherapy, in particular, use of a chimeric antigen receptor targeting CD147 for treating cancer.SELECTED DRAWING: None

Provided is a humanized CD19 single-chain variable fragment (scFv) having a mutation of valine to glycine in CDR1, comprising VH having the amino acid sequence of SEQ ID NO: 6 and VL having the amino acid sequence of SEQ ID NO: 5. Also provided is a CD19 chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv), (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized CD19-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 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.

To provide improved therapeutic approaches for treating small cell lung cancer (SCLC) and other DLL3 (delta-like ligand 3)-expressing cancers.SOLUTION: Provided is a chimeric antigen receptor (CAR) comprising a DLL3-binding domain, the DLL3-binding domain comprising or being derived from a single domain antibody (sdAb) or a single chain variable fragment (scFv).SELECTED DRAWING: None

To provide multispecific antigen-binding proteins for engaging NK cells for triggering NK cell cytotoxicity by engaging CD16A (FcγRIIIA) expressed on the NK cells.SOLUTION: A multispecific antigen-binding protein comprises: (a) two target antigen-binding moieties each comprising a Fab fragment and an Fc portion, and (b) two CD16A antigen-binding moieties each in the format of a single chain variable fragment (scFv) comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the variable region at the N-terminus of each of the two scFvs is the VL, wherein the N-terminus of the first of the two scFvs is fused to the C-terminus of the Fc portion of the first target antigen-binding moiety of the two target antigen-binding moieties, and the N-terminus of the second of the two scFvs is fused to the C-terminus of the Fc portion of the second target antigen-binding moiety of the two target antigen-binding moieties.SELECTED DRAWING: Figure 1

The present disclosure provides conjugates comprising a targeting moiety, such as an antibody, Fab fragment or single chain variable fragment (ScFv), and a lipid nanoparticle (LNP) encapsulating a therapeutic agent (i.e., payload) wherein the targeting moiety, such as an antibody, Fab fragment or ScFv, is conjugated to the lipid nanoparticle via a linker, and wherein the linker comprises an enzyme recognition sequence and a click product formed by a click reaction between a first click handle on the targeting moiety such as an antibody, Fab fragment or ScFv and a second click handle on the LNP.

The present invention relates to the field of biotechnology, and in particular to a bispecific antibody and its application. The present invention provides a bispecific antibody with neutralizing activity against SARS-CoV-2 mutants (VOCs) and SARS-related coronaviruses (SARSr-CoVs). The bispecific antibody is constructed by fusing the single-chain variable fragments of the two antibodies via a GS linker. The bispecific antibody exhibits high binding ability to S1 and has broad-spectrum and high-efficiency activity against pseudovirus SARS-CoV-2 variants and SARS-related coronaviruses, indicating that the bispecific antibody provided by the present invention has the potential to prevent and treat SARS-CoV-2 and SARS-related coronaviruses.

Disclosed herein are antibodies that selectively bind to EGFR and CD3, wherein the anti-EGFR domain is in the form of a Fab or Fab'antibody linked to a single chain variable fragment (scFv) that binds to CD3. Bispecific antibody forms of Fab or Fab'linked to scFv provide potency and safety advantages over other bispecific antibody forms, Provided herein are antibodies that selectively bind to EGFR and CD3, pharmaceutical compositions thereof, and methods of producing such antibodies.

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 provides: ferritin; a single-chain variable fragment bound to the N-terminus of the ferritin; and a fusion protein self-assembling nanoparticle structure in which an N-terminus RNA-interaction domain (RID) in a human-derived lysyl-tRNA synthetase is bound to the N-terminus of the single-chain variable fragment by means of a novel fusion partner. Therefore, the present invention provides: a fusion protein having enhanced water solubility; nanoparticles; a vector coding same; a host cell transformed by means of the vector, and a pharmaceutical composition, for treating a disease, using the same.

The present disclosure provides conjugates comprising a targeting moiety, such as an antibody, Fab fragment or single chain variable fragment (ScFv), and a lipid nanoparticle (LNP) encapsulating a therapeutic agent (i.e., payload) wherein the targeting moiety, such as an antibody, Fab fragment or ScFv, is conjugated to the lipid nanoparticle via a linker, and wherein the linker comprises an enzyme recognition sequence and a click product formed by a click reaction between a first click handle on the targeting moiety such as an antibody, Fab fragment or ScFv and a second click handle on the LNP.

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.

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 invention relates to an immunoglobulin derived single-chain fragment variable (scFv) that broadly binds HLA II molecules and uses thereof. In particular, targeting of an antigen to antigen presenting cells with the HLAII-specific targeting unit provided herein find use in enhancing immune responses after vaccination.

Provided are an anti-HER2 / PD1 bispecific antibody, preparation method, and antitumor application. Specifically, a single-chain variable fragment scFv and an immunoglobulin antibody IgG are connected by means of a peptide linker to obtain a bispecific antibody; the bispecific antibody can simultaneously target the tumor cell surface molecule HER2 antigen and T lymphocyte surface molecule PD-1. The results of experimentation show that the bispecific antibody provided is capable of inhibiting the proliferation of HER2-positive tumor cells while also blockading the binding of PD-1 / PD-L1, releasing the suppressive state of T cells and performing an antitumor function.

Inventors followed an untargeted approach by screening a single chain variable fragment (scFv) library via phage display against recombinant human full-length wild-type (wt)TDP-43. They identified four wtTDP-43-specific scFv, two of which were retained following cellular expression and colocalization with TDP-43 in vitro. In silico binding site prediction on TDP-43 suggested the pathologically-relevant C-terminal and RRM1 domains as potential targets. One scFv diminished the amount of the insoluble 35-kDa C-terminal fragment of TDP-43 when the wildtype protein was overexpressed. Another scFv inhibited NF-κB activation associated with TDP-43 overexpression. Both scFv seemed to reverse some metabolic alterations caused by TDP-43 overexpression. Their findings offer two scFv molecules that bind wtTDP-43, alter its aggregation, and modify cellular pathways associated with TDP-43 proteinopathies. Accordingly, the present invention relates to scFv intrabodies targeting TDP-43 and their uses in diagnosis and treatment methods.

Disclosed herein are recombinant polypeptides and recombinant nucleic acids encoding the same. According to some embodiments of the present disclosure, the recombinant polypeptide comprises a first bi-functional domain, and a first single-chain fragment variable (scFv) or a peptide linked to the N-terminus of the first bi-functional domain. Optionally, the recombinant polypeptide further comprises a second scFv linked to the N-terminus of the first scFv or peptide. Also disclosed herein are methods of treating cancers by using the immune cells expressing the recombinant polypeptides.

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 present invention provides a chimeric antigen receptor, a nucleic acid molecule, CAR-Ms, and applications thereof, and belongs to the field of biomedical engineering and peptides. The chimeric antigen receptor provided by the present invention comprises a CD8 α leader signal peptide, a single-chain variable fragment, a CD8 α hinge, a CD8 transmembrane domain, and an intracellular co-stimulatory signal transduction domain. The single-chain variable fragment can target any known antigen; the intracellular co-stimulatory signal transduction domain is any one or a combination of TLR2, TLR4, TLR7, Mincle, Dectin-1, NOD2, CD40, 4-1BB, OX40, and CD3ζ. The present invention also provides a macrophage-targeted nanogel for RNA delivery. Macrophages transfected with the nanogel system express chimeric antigen receptors, which can achieve specific targeting and phagocytosis of known antigen-positive (e.g., MUC1) tumor cells.

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.

In aspects, a chimeric cytokine receptor (CCR) is provided that comprises (i) a single chain variable fragment (scFv) which specifically binds to an antigen, one or more extracellular interleukin receptor domains, an interleukin receptor transmembrane domain, and an interleukin receptor intracellular domain; and (ii) a single chain variable fragment (scFv) which specifically binds to an antigen, one or more extracellular interleukin receptor common gamma chain (γc) domains, a γc transmembrane domain, and a γc intracellular domain.