3487results about "Fusions for specific cell targeting" patented technology

Aspects of the disclosure relate to compositions comprising a plurality of complexes comprising an antibody (e.g., anti-TfRI antibody) covalently linked to one or more oligonucleotides (e.g. a DMPK targeting oligonucleotide), each oligonucleotide being covalently linked at a linkage site represented by a lysine (K) residue of the antibody. In some embodiments, the antibody comprises a heavy chain comprising a heavy chain variable region (VH) and a heavy chain constant region, and a light chain comprising a light chain variable region (VL) and a light chain constant region, wherein at least 80% (e.g., 80%-98%, 80%-95%, 80%-90%, 85%-98%, 85%-95%, 85%-90%, 90%-98%, 90%-95%, 95%-97%, or more) of the light chain constant regions of the antibodies of the complexes in the composition are independently covalently linked to an oligonucleotide at a linkage site represented by K188 (based on Kabat numbering) and / or a linkage site represented by K190 (based on Kabat numbering) of the light chain constant regions of the antibodies.

The invention provides compositions and methods for treating diseases such as cancer. The invention also relates to a method of administering a therapy comprising a chimeric antigen receptor, an IL-15R molecule and an IL-15 molecule.

The invention provides a method of treating an adult subject having a hematological cancer, comprising administering to the subject selected dosage regimens comprising a plurality of immune effector cells expressing a CAR molecule.

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.

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 invention belongs to the technical field of biology, and provides a nanometer antibody targeting Nectin-4, and a nucleic acid molecule and an expression vector for coding the nanometer antibody targeting Nectin-4. The invention also provides a chimeric antigen receptor which comprises an extracellular antigen binding domain, a transmembrane domain and an intracellular domain, and the extracellular antigen binding domain is a Nectin-4 nano antibody; the invention also provides a chimeric antigen receptor CAR which contains the nano antibody as scFv and co-expresses CXCR1, a CAR-T cell constructed by the chimeric antigen receptor CAR, and an enhanced CAR-T cell obtained by modifying the CAR-T cell with microbial short-chain fatty acid, so as to improve the infiltration and anti-tumor activity of the CAR-T cell targeting Nectin-4.

The invention relates to the technical field of biological medicine, and provides a targeting exosome capable of delivering nucleic acid drugs and a preparation method of the targeting exosome. The exosome comprises a fusion polypeptide, the fusion polypeptide comprises a targeting protein molecule, an exosome transmembrane protein and a nucleic acid binding domain, and the exosome can load a nucleic acid molecule through binding of the nucleic acid binding domain. According to the invention, engineering modification is carried out on the exosome, so that nucleic acid molecules can be efficiently loaded into the exosome, and meanwhile, the exosome is endowed with the capability of targeting to specific target cells, tissues and organs.

Compositions and methods for treating diseases associated with aberrant glycosylation of cell surface molecules and expression of tumor-associated carbohydrate antigens (TACAs) are provided. Also provided are fusion proteins having specificity for tumor-associated carbohydrate antigen (TACA) comprising a half-life extender molecule, vectors encoding the TACA-fusion proteins, and recombinant cells comprising the TACA-specific fusion proteins.

The disclosure provides interleukin 21 (IL-21) variants that have (i) decreased or no binding to a human interleukin 21 receptor (IL-21R) as compared to a wild-type human IL-21 polypeptide; or (ii) increased stability as compared to a wild-type human IL-21 polypeptide; or (iii) decreased or no binding to a human interleukin 21 receptor (IL-21R) as compared to a wild-type human IL-21 polypeptide and increased stability as compared to a wild-type human IL-21 polypeptide. The disclosure also provides fusion proteins including an antibody or fragment thereof bound, e.g., covalently linked, to an IL-21 variant.

The present disclosure provides compositions and methods comprising recombinant particles suitable for specifically delivering one or more chimeric antigen receptors to immune effector cells in vivo.

The present disclosure provides compositions comprising antigen binding polypeptides. More particularly, the disclosure relates to polypeptides comprising antibodies or antigen binding fragments thereof, nucleic acids encoding the polypeptides, and vectors for expressing the same.

The present disclosure provides compositions comprising antigen binding polypeptides. More particularly, the disclosure relates to polypeptides comprising antibodies or antigen binding fragments thereof, nucleic acids encoding the polypeptides, and vectors for expressing the same.

The present disclosure provides compositions comprising antigen binding polypeptides. More particularly, the disclosure relates to polypeptides comprising antibodies or antigen binding fragments thereof, nucleic acids encoding the polypeptides, and vectors for expressing the same.

The present disclosure provides compositions comprising antigen binding polypeptides. More particularly, the disclosure relates to polypeptides comprising antibodies or antigen binding fragments thereof, nucleic acids encoding the polypeptides, and vectors for expressing the same.

The invention relates to an anti-DLL3 nano antibody, a chimeric antigen receptor and application of the anti-DLL3 nano antibody and the chimeric antigen receptor. Specifically, the invention provides a nano antibody specifically binding to DLL3 or an antigen binding fragment thereof, provides a chimeric antigen receptor related to the nano antibody or the antigen binding fragment thereof, a polynucleotide, a recombinant vector, a host cell, an antibody, an antibody conjugate, a pharmaceutical composition and a kit, and also provides related uses and methods.

The invention provides a preparation method of a PSR.Syn.CD19. BCMA CAR-T cell as well as the cell and application of the PSR.Syn.CD19. BCMA CAR-T cell, the PSR.Syn.CD19. BCMA CAR-T cell is characterized in that after the CAR-T cell and a CD19 antigen positive tumor cell are co-incubated, the expression of an effector molecule BCMA-CAR can be induced, and if the tumor cell simultaneously expresses a BCMA antigen, the CAR-T cell capable of killing a tumor can be identified. Experimental results show that the cell prepared by the method can efficiently and specifically kill tumor cells, has a persistent killing effect and has a safety switch capable of starting a killing function. In addition, the tumor can be specifically killed, the cell proliferation rate is high, and the proliferation rate under the stimulation of tumor cells is higher than that of a PAN-T group.

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

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.

An antigen targeting, anti-CD16A, and immune effector cell activating trifunctional fusion protein has a CD16A binding region that specifically binds to CD16A, a tumor-associated antigen (TAA) binding region that specifically binds to a TAA, an IL-15 / IL-15Ra complex formed by combining IL-15 and IL-15Ra, and an Fc domain. A designed tumor-targeting innate immune cell activation molecule, i.e., an anti-TAA, anti-CD 16A, and cytokine IL 15 trifunctional fusion protein targets NK cells to a tumor by simultaneously binding to a TAA on tumor cells and CD16A on NK cells, so that the NK cells release perforin and granzymes to induce apoptosis and cause tumor cell death. The cytokine IL15 expands and maintains the function of the NK cells, stimulates immune cell proliferation, and changes the immune microenvironment of the tumor.

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

Aspects described herein pertain to engineered chimeric antigen receptors (CARs) and compositions thereof having specificity and affinity for fluorescein containing ligands presented on the surface of tumor cells. Also provided herein are compositions including CARs further comprising a spacer arm and methods of making and using these compositions.

Provided herein, among other things, are polynucleotides comprising a nucleic acid encoding an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) and natural killer cells expressing the polynucleotides.

The present invention provides an antibody binding to human CD73, a preparation method therefor, and a use thereof. The monoclonal antibody of the present invention can bind to a CD73 antigen with high specificity, has high affinity, has remarkable anti-tumor activity and the like, and has excellent clinical application prospects.

Provided is a recombinant human serum albumin-collagen binding domain (CBD) fusion protein for tumor-specific targeting matrix and its use in specific targeted treatment of a solid tumor. HSA and the CBD generate gene fusion in the form of different molecular structures, and can be expressed in a constructed recombinant engineered host. A pharmaceutical recombinant fusion protein is obtained through large-scale fermentation. The recombinant fusion protein shows tumor-specific targeting of solid tumors and can be used as a starting material of a broad-spectrum matrix carrier. The recombinant fusion protein is coupled with any tumor treatment drug, small-molecule compound, or cytotoxic protein to form an innovative pharmaceutical composition. The pharmaceutical composition of the recombinant fusion protein is also long-acting, can prolong a half-life of the conjugate drug in vivo, and has a significantly better clinical curative efficacy on anti-tumor than that of a monomer drug.

The invention discloses a Trop2 targeting chimeric antigen receptor macrophage as well as a preparation method and application thereof. The macrophage contains a specific CAR (chimeric antigen receptor) targeting Trop2 and a blocking agent for blocking an immunosuppression signal; the amino acid sequence of the Trop2 specific CAR targeting the breast cancer is as shown in SEQ ID NO. 1; the nucleotide sequence of the mRNA of the specific CAR of the targeted Trop2 is as shown in SEQ ID NO. 2. According to the invention, LNP is adopted to co-deliver CAR mRNA and TLR agonists, and macrophages are edited in vivo to generate CAR-macrophages expressing Trop2 in situ, so that a tedious engineering cell in-vitro preparation process is omitted, and potential whole-body toxic and side effects caused by immune cell system reinfusion are avoided.

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The invention relates to the technical field of immunotherapy, and provides a GPRC5D-targeted single-domain antibody, a chimeric antigen receptor and application of the GPRC5D-targeted single-domain antibody and the chimeric antigen receptor. Specifically, the invention provides a GPRC5D-targeted single-domain antibody, a GPRC5D-targeted chimeric antigen receptor (CAR) constructed by using the single-domain antibody, and an engineered immune effector cell containing the CAR. The invention also provides a single-domain antibody targeting GPRC5D, a chimeric antigen receptor and an application of the engineered immune effector cell containing the CAR in preparation of drugs for diagnosis, prevention and / or treatment of diseases or symptoms related to GPRC5D expression.

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.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.