1841results about "Fusions for specific cell targeting" patented technology

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK / NK-92 cells.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer suppress alloreactive donor cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

The invention provides immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions and methods thereof.

The invention provides a monoclonal antibody targeting a human folate receptor alpha subtype. Specifically, a mouse is immunized through FR1 recombinant protein, and a monoclonal antibody with high affinity to FR1 is screened out. In addition, the invention also provides an amino acid sequence of the monoclonal antibody, nucleic acid containing the sequence, a carrier or a conjugate containing the nucleic acid, and application of the monoclonal antibody in FR1 overexpressed tumors / cancers.

Provided are nucleic acids that encode decoy-resistant interleukin 18 (DR-18) polypeptides, as well as vectors and cells comprising such nucleic acids and cells that comprise such vectors. Cells encoding DR-18 polypeptides may be referred to as DR-18 armored cells. The nucleic acids may further encode a chimeric antigen receptor (CAR) or multiple CARs, including CARs that bind to antigens described herein. Methods are also provided, including methods of making the nucleic acids, vectors, and / or cells, as well as methods of use, such as employing the nucleic acids, vectors, and / or cells, in the treatment of a subject having cancer.

Aspects of the disclosure relate to complexes comprising an anti-TfR1 antibody covalently linked (e.g., via a linker such as a peptide linker) to a lysosomal enzyme (e.g., an acid alpha glucosidase enzyme), and methods of making and using the fusion complexes to treat a lysosomal storage disease (e.g., Pompe disease).

The invention provides a CLDN6 single domain antibody and a humanization method thereof. The CLDN6 single-domain antibody provided by the invention has targeted specificity to CLDN6, only recognizes the CLDN6 and does not recognize CLDN3, CLDN4 and CLDN9 of the same family, or the recognition modes are obviously different. The CLDN6 single-domain antibody 1H07 with targeting specificity provided by the invention can be used for constructing a chimeric antigen receptor (CAR) and a bivalent antibody (bispecific antibody). The CAR constructed based on the antibody sequence can be transduced into a T cell to create a CAR-T cell specifically targeting CLDN6, and the CAR-T cell can be used for treating solid tumors such as ovarian cancer.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Chimeric antigen receptors that include an antigen recognition domain; a spacer domain derived from a modified immunoglobulin Fc region having one or more mutations in its CH2 region resulting in impaired binding to an FcR; and an intracellular signaling domain.

The present application is directed to methods and compositions that are useful for reducing the number of myeloid-derived suppressor cells (MDSC), tumor associated macrophages (TAM), or both in a subject. The methods include administering an antigen binding protein that binds to an antigen expressed by MDSC and / or TAM, or administering a modified T cell or NK-92 cell that expresses an antigen binding protein that binds to an antigen expressed by MDSC and / or TAM, or a combination of both, to a subject. For example, the antigen binding protein can bind to CD33 expressed by MDSC and / or TAM. The methods and compositions are useful for treating a disease associated with MDSC and / or TAM infiltration into a tissue or tumor.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

Provided herein are chimeric receptors, including chimeric antigen receptors (CARs), comprising BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof, including heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, including a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof including in adoptive cell therapy.

The invention relates to the technical field of biology, and particularly discloses a recombinant protein for improving the curative effect of an ADC drug and application of the recombinant protein. The recombinant protein comprises a tumor cell surface targeting structure, a cell transmembrane structure and toxin molecules, the toxin molecule is connected and fused with the tumor cell surface targeting structure and / or the cell transmembrane structure; the tumor cell surface targeting structure is a protein structure capable of being specifically combined with a tumor cell surface target spot; and the cell penetrating structure is a protein structure for mediating the recombinant protein to penetrate through a cell membrane to enter the cell. The tumor cell surface targeting structure is used for specifically recognizing a target cell surface target spot, the killing activity of a conventional antibody is brought into play, then toxin molecules are brought into tumor cells through the cell transmembrane structure, toxin is released, the tumor killing effect is achieved, the ADC drug curative effect is improved, and the ADC drug application prospect is wide. The transmembrane efficiency of the cell transmembrane structure can be improved to 50-90%, so that the traditional ADC drug treatment window is improved.

The present application provides chimeric proteins comprising an antibody moiety that specifically binds to a component of an influenza virus or a variant thereof, and a positively charged mucoadhesive peptide fragment. Compositions comprising the chimeric proteins described herein are useful for preventing or treating an infection caused by an influenza virus or a variant thereof in an individual.

The present disclosure provides a PD1 targeted novel IL-2 VitoKine composition, featuring a high-affinity PD1 antibody domain and a bio-activable IL- 2 domain with optimally reduced potency. The PD1 Ab-IL2 VitoKine platform mitigates IL-2 therapy-related toxicities and synergizes the anti-tumor effects of PD1 and IL- 2 by: 1) efficiently targeting an inert IL-2 directly to tumor-infiltrating lymphocytes (TILs); 2) ensuring highly tumorspecific activation of the IL- 2 domain by TME- enriched proteases that co-localized with TILs; 3) allowing PD1 Ab and activated IL- 2 to act on intratumoral CD8+T cells in cis. The VitoKine demonstrates greatly enhanced concealment efficiency and has a lower intrinsic basal activity than what would typically be expected from the VitoKine platform incorporating a non-attenuated IL-2. This improvement permits a substantially higher dose tolerance, enabling safe administration at efficacious dose levels of the PD1 antibody, reversing T- cell anergy or exhaustion and further synergizing with IL-2 mediated anticancer immune response.

The present invention provides a chimeric antigen receptor (CAR) that recognizes CSPG4 as well as methods of use in the treatment of diseases and disorders.

Disclosed are VHH chimeric antigen receptors (VCARs), VCAR transposons encoding VCARs of the disclosure, cells modified to express VCARs of the disclosure, as well as methods of making and methods of using the same for adoptive cell therapy.

Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from an anti-ROR-1 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders.

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

An improved method of treating cancers with engineered T cells is described.

Provided are complementarity determining regions (CDRs) of the VHH chain of an anti-PD-L1 single domain antibody, wherein the CDRs of the VHH chain comprise the following: CDR1 having the amino acid sequence set forth in SEQ ID NO:5n+1; CDR2 having the amino acid sequence set forth in SEQ ID NO:5n+2, or a CDR2 having an amino acid sequence which has greater than 85% sequence identity to the sequence set forth in SEQ ID NO:2; and CDR3 having the amino acid sequence set forth in SEQ ID NO:5n+3, where each n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

Compositions and methods for treating diseases associated with expression of a cancer associated antigen are disclosed. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, SHP inhibitory molecules, vectors encoding the same, and recombinant immune effector cells comprising the CARs and SHP inhibitory molecules. Methods of administering a genetically modified immune effector cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen and a SHP inhibitory polypeptide are also disclosed.

The invention belongs to the technical field of biology, and particularly relates to an anti-porcine reproductive and respiratory syndrome virus antibody or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof can specifically recognize and bind the porcine reproductive and respiratory syndrome virus or the GP4 protein thereof, and has good affinity with the porcine reproductive and respiratory syndrome virus or the GP4 protein thereof; the compound can be used for preparing products for diagnosing, preventing and / or treating porcine reproductive and respiratory syndrome virus infection or diseases caused by porcine reproductive and respiratory syndrome virus infection, detecting existence or level of porcine reproductive and respiratory syndrome virus or GP4 protein thereof in a sample or screening drugs for preventing and / or treating porcine reproductive and respiratory syndrome virus infection or diseases caused by porcine reproductive and respiratory syndrome virus infection.

The invention is directed to a chimeric antigen receptor (CAR) directed against CD19, which comprises an amino acid sequence of any one of SEQ ID NO: 1-SEQ ID NO: 13. The invention also provides T-cells expressing the CAR and methods for destroying malignant B-cells.

The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

The present invention relates to a fusion protein comprising an antibody against T cell surface molecule, interleukin-2 and a Fc region of an immunoglobulin. The fusion protein is a heterodimer or homodimer. The present invention also relates to use of the fusion protein in the manufacture of an anti-tumor drug.

Featured are polypeptides that include soluble alkaline phosphatases, mutants, fragments, fusion proteins thereof, and methods of use thereof, for treating bone mineralization disorders, such as hypophosphatasia (HPP), and symptoms thereof. The polypeptides include a soluble alkaline phosphatase (sALP) or fragment thereof, which is derived from a naturally occurring alkaline phosphatase (ALP).

The present invention relates to chimeric antigen receptors (CAR) against multiple but not all human leukocyte antigen (HLA-G) isoforms. More specifically, the invention concerns CARs that are specific for HLA-G β2M-free or β2M-associated immunosuppressive isoforms respectively.