1722 results about "CD3" patented technology

The invention belongs to the field of molecular biology and immunology, and particularly relates to an anti-CD3 nano antibody capable of activating the activity of T cells as well as a preparation method and application of the anti-CD3 nano antibody. The invention provides a preparation method of the anti-CD3 nano antibody. The preparation method comprises the following steps: constructing a CD3 plasmid and an overexpression cell line, and immunizing alpaca to obtain peripheral blood mononuclear cells (PBMC) of the alpaca; extracting RNA (Ribonucleic Acid) and carrying out reverse transcription to obtain cDNA; carrying out PCR amplification on the antibody gene segment and cloning the antibody gene segment to a phage display vector; and electrically transforming the vector into SS320 competent cells to obtain the nano antibody library. After two rounds of panning, detecting and screening an antibody clone capable of being combined with the CD3 protein through ELISA (Enzyme-Linked Immunosorbent Assay); an antibody sequence is selected through sequencing, and an antibody protein is expressed by using a mammalian cell high-throughput expression system; and then detecting and screening the antibody which is only specifically combined with the CD3. The method disclosed by the invention is simple, convenient and rapid to operate, and can be used for preparing active antibodies for treating potential tumors and proliferative diseases.

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 provides an in-vitro culture method of T cells, and belongs to the technical field of genetic engineering.The culture method comprises the steps that immune cell serum-free culture media are added into peripheral blood mononuclear cells, and activated culture is conducted in the presence of cell factors to obtain activated T cells; the cell factor comprises an IL-2 monoclonal antibody and a CD3 monoclonal antibody, and further comprises two or three of an iCAM1 protein, a CCL21 protein and OK432. The T cells obtained through activation and multiplication culture are relatively stable in cell phenotype, relatively large in amplification multiple, relatively high in cell viability and relatively high in tumor killing efficiency. T cells are obtained after activation is performed for 24 hours and then multiplication culture is performed for 14 days, and the number of the cells is 6.2-8.9 * 10 < 9 >; the killing rate on Hela cells is 51.9 to 74.1 percent, and the killing rate on LOVO cells is 55.7 to 80.5 percent.

The invention provides BiTE for tumor targeted immunotherapy and a preparation method and application, and relates to the technical field of biological pharmacy, the BiTE is obtained by coupling a nano antibody and fusion protein, the C terminal of the nano antibody contains an amino acid sequence SEQ ID No.3, and the BiTE has the function of targeting a human epidermal growth factor receptor on tumor cells; the fusion protein also targets a CD3 receptor on a T cell, activates the T cell, connects the T cell with a tumor cell in time and space, activates the T cell, secretes perforin and granzyme B to kill the tumor cell, and plays a role in targeted immunotherapy. The isopeptide bond is used for coupling the nano antibody and the fusion protein, coupling can be completed within 15 min, the coupling efficiency is 100%, and the in-vivo half-life period of the nano antibody can be prolonged by 6 times.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

Disclosed herein are bispecific antibodies against FOLR1 and uses thereof, particularly bispecific antibodies against FOLR1 and CD3, nucleic acids encoding the antibodies, vectors comprising the nucleic acids, and host cell comprising the nucleic acids or the vectors. Also disclosed are pharmaceutical compositions and antibody-drug conjugates comprising the antibodies, and therapeutic methods by using the antibodies.

Provided herein are novel anti-CD20 x anti-CD28 antibodies and methods of using such antibodies for the treatment of B-cell malignancies. Subject anti-CD20 x anti-CD28 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and CD20 on tumor cells. Thus, such antibodies enhance anti-tumor activity at tumor sites. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3 x anti-CD20 x anti-CD79b antibodies) for the treatment of B-cell malignancies.

Provided by the present invention are a bispecific T-cell engager, recombinant oncolytic virus thereof, and use thereof. The present invention provides an αCD47 and αCD3 bispecific T-cell engager. The present invention also provides an isolated nucleic acid molecule that encodes said bispecific T-cell engager. The present invention also provides an expression framework of said bispecific T-cell engager BiTE. The present invention also provides a recombinant oncolytic virus, and said oncolytic virus is operably inserted with or contains the expression framework of said bispecific T-cell engager BiTE. In the present invention, the bispecific T-cell engager is combined with the oncolytic virus, and in comparison with pure gene therapy or virotherapy, the oncolytic virus significantly enhances the inhibition capability on malignant tumors.

Disclosed are lipid nanoparticle (LNP) delivery systems that specifically target T cells. The LNP delivery system comprises antibodies conjugated to the surface of the LNP, e.g., via maleimide chemistry, that target at least two T cell surface proteins, e.g., CD3 and CD28. The LNP delivery system can have a single population of LNP conjugated to either a bispecific antiCD3 / antiCD28 antibody, or two monospecific antiCD3 and antiCD28 antibodies, or two populations of LNP wherein each population comprises a monospecific antibody. The payload of the LNP delivery system can be, e.g., mRNA encoding chimeric antigen receptors (CAR), a linear DNA fragment or a plasmid encoding chimeric antigen receptors (CAR) or therapeutic proteins such as antibodies, components of a gene editing systems (e.g., CRISPR-Cas), small molecules, antibody-drug conjugates (ADC), and any combination thereof, either encapsulated in the LNP or attached to its surface (e.g., conjugated). Also provided are lipids, pharmaceutical compositions, kits, and methods of treatment.

The use of dual-target CAR-T cells in treating systemic lupus erythematosus and other B-cell autoimmune diseases is provided. The first target of the chimeric antigen receptor is CD19, the second target is BCMA, and specifically, the chimeric antigen receptor is a chimeric antigen receptor with a Loop structure, which is shown as follow: L-VL, CD19-VH, BCMA-VL, BCMA-VH, CD19-H-TM-C-CD3ζ; the BCMA-CD19 CAR-T cells transduced by the chimeric antigen receptor targeting CD19 and BCMA can completely block the pathway of producing autoantibodies, and completely cover the B cells, plasmablasts and plasma cells at multiple differentiation stages that produce autoantibodies, so that the dual-target CAR-T therapy designed based on this concept can be aimed at refractory SLE and is expected to achieve faster remission and deeper and lasting curative effect.

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.

The present invention relates to bispecific antibodies (bsAbs) and the use of such antibodies in the treatment of disease in subjects. Moreover, advantageous treatment regimens are provided for the treatment of B-cell Non-Hodgkin Lymphoma (B-NHL).

The invention provides methods of dosing for the treatment of cancers, such as B cell proliferative disorders, with anti-cluster of differentiation 20 (CD20) / anti-cluster of differentiation 3 (CD3) bispecific antibodies.

The invention belongs to the technical field of tumor micro-immune environments, and particularly relates to a kit for detecting a tumor micro-environment, a detection method and application, the kit comprises rare metal element labeled monoclonal antibodies, the rare metal element labeled monoclonal antibodies comprise 115In-CD20, 139La-Histone H3, 142Nd-CD56, 144Nd-CD14, 146Nd-Vimentin, 148Nd-Pan-CK, 151Eu-CD31, 156Gd-CD4, 158Gd-E-Cadrin, 159Tb-CD68, 162Dy-CD8a, 166Er-CD45, 167Er-CD15, 170Er-CD3, 171Yb-CD11c and 209Bi-alpha-SMA, and the rare metal element labeled monoclonal antibodies comprise The invention can be used for simultaneously detecting and researching the quantity, positioning and spatial topological relation of each cell component in a tumor microenvironment, and provides a multi-immunofluorescence detection kit and method for ubiquitous epithelial differentiation-derived tumors based on an imaging mass spectrum flow technique. A plurality of biomarkers can be analyzed at the same time by using multiple immunohistochemical staining and rare earth metal tag signal detection technologies, so that the aim of performing high-dimensional analysis on a tumor microenvironment is fulfilled according to cell composition, functional state and cell-cell space interaction relationship.

The invention relates to a culture method for activating NKT cells by DC cells in vitro and application of the NKT cells. The preparation method of the NKT cell comprises the following steps: activating a DC cell by using cell inducing factors such as alpha-GalCer, GM-CSF and IL-4, co-culturing the DC cell and a cryopreserved and resuscitated suspension cell left after adherent sorting, and activating and amplifying the NKT cell. The proportion of NKT (CD3 + CD56 +) prepared by the invention is more than 80%, and a small amount of iNKT cells are contained at the same time.

The invention belongs to the field of biological medicine, and relates to a pharmaceutical composition of an anti-CD3 * CD20 bispecific antibody, in particular to a liquid preparation and a freeze-dried preparation of the bispecific antibody and medical application of the liquid preparation and the freeze-dried preparation. More specifically, the pharmaceutical composition contains an anti-CD3 * CD20 bispecific antibody, a buffer solution, a stabilizer and a surfactant, the pH value of the pharmaceutical composition is about 4.5-6.5, and the pharmaceutical composition has good stability.

The invention discloses a kit and method for detecting leukemia and lymphoma based on full-spectrum flow cytometry, the kit comprises 25 antibodies, the antibodies are specifically bound with fluorescein respectively, and leukemia and lymphoma are detected through full-spectrum flow cytometry; the 25 kinds of antibodies comprise HLA-DR (human leukocyte antigen-DR), CD38, CD7, CD34, Lambda, CD19, CD64, CD14, CD5, CD123, CD16, CD20, Kappa, CD117, CD13, CD45, CD11b, CD2, CD10, CD8, CD15, CD4, CD3, CD56 and CD33. The kit comprehensively covers development stages of various lines of bone marrow cells, and common abnormal expressions of various leukemia, myelodysplastic syndromes and lymphoma, and can preliminarily screen various leukemia and lymphoma.

A bispecific or dual target CAR or CAR-T cells can be used to treat and / or prevent an autoimmune disease. The bispecific CAR may target CD19 and BCMA. The CAR may have a loop structure, which is shown as follow: L-VL, CD19-VH, BCMA-VL, BCMA-VH, CD19-H-TM-C-CD3ζ; the BCMA-CD19 CAR-T cells transduced by the chimeric antigen receptor targeting CD19 and BCMA can completely block the pathway of producing autoantibodies, and completely cover the B cells, plasmablasts and plasma cells at multiple differentiation stages that produce autoantibodies, so that the dual-target CAR-T therapy designed based on this concept can be aimed at refractory SLE and is expected to achieve faster remission and deeper and lasting curative effect.

Provided are a fusion protein (for example, in the form of a bispecific antibody) binding to CD235a and CD3, a preparation method therefor, and a related use thereof.

The present disclosure relates to a method for ameliorating or treating malignant ascites using an anti-EpCAM × CD3 bispecific antibody and a composition thereof and use of the anti-EpCAM × CD3 bispecific antibody and a composition thereof in ameliorating or treating malignant ascites. The present disclosure features better dosing convenience, longer dosing intervals, longer dosing cycles, and improved efficacy and safety.

A bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. A nucleic acid comprising a polynucleotide encoding the antibody construct, a vector comprising the nucleic acid comprising the polynucleotide and a host cell transformed or transfected with the nucleic acid comprising the polynucleotide or vector. A process for the production of the antibody construct, a medical use of the antibody construct in the treatment of melanoma, and a kit comprising the antibody construct.

The present disclosure relates to antigen binding molecules that specifically bind to DLL3 and CD3, which can be used in the treatment of cancer, and medical uses thereof.

An antibody capable of binding to LILRB4 and a bispecific antibody capable of binding to LILRB4 and CD3 are provided. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. Also provided are methods of treating solid tumors, multiple myeloma or leukemia, such as acute myelogenous leukemia (AML), using the anti-LILRB4xCD3 double antibodies of the present invention.

The present invention relates to novel DLL3 / CD3 binding proteins. The invention also relates to nucleic acids encoding such proteins; to methods for preparing such proteins; to host cells expressing or capable of expressing such proteins; to compositions comprising such proteins; and to uses of such proteins or such compositions, in particular for therapeutic purposes in the field of cancer diseases.

The invention discloses construction and application of a targeted exosome chimeric antigen receptor molecule for treating HIV (human immunodeficiency virus) infection, and belongs to the technical field of biological medicines. According to the invention, the mRNA for coding the anti-HIV CAR is directionally packaged into the targeting exosome. Nanometer antibody sequences of CD3, CD4 and CD8 < + > T receptors on targeted T cells are fused to the N terminal of LAMP-2B to construct a specific targeting plasmid, so that targeting peptides are expressed on the surface of an exosome membrane, expression plasmids containing RNA binding protein L7A and exosome tag protein CD63 are constructed, and HEK293F cells are co-transfected by the expression plasmids and CAR plasmids containing C / D box to obtain the exosome loaded with CAR mRNA and targeted to the T cells. When the exosome is incubated with PBMC (peripheral blood mononuclear cells) in vitro or is transfused back into a humanized mouse body, human CAR-T cells can be constructed, and the exosome has remarkable activity of killing virus infected cells.

The invention provides a bispecific antibody targeting CD3 and tumor targets and application thereof. The bispecific antibody comprises a first antigen binding region, a second antigen binding region and an Fc part, the Fc part comprises a first Fc peptide fragment and a second Fc peptide fragment; the first antigen binding region comprises an scFv fragment and a binding protein of a first molecule or a fragment thereof, the binding protein of the first molecule or the fragment thereof is connected with the N end of the scFv fragment, and the C end of the scFv fragment is connected with the N end of the first Fc peptide fragment; the second antigen binding region comprises a binding protein of a second molecule or a fragment thereof, and the binding protein of the second molecule or the fragment thereof is connected with the N end of the second Fc peptide fragment; the first molecule and the second molecule are the same, and the scFv fragment has CD3 binding activity. The bispecific antibody is weak in combination with T cells, strong in combination with tumor cells, good in safety, high in anti-cancer activity and high in clinical application and drug development value.

The present invention generally relates to antibodies that bind to CD3 and CD19, e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease.

Provided are methods of clinical treatment of Diffuse Large B-cell Lymphoma (for example, relapsed and / or refractory Diffuse Large B-cell Lymphoma) in human subjects using a bispecific antibody which binds to CD3 and CD20 in combination with lenalidomide or ibrutinib and lenalidomide.

Provided are multispecific antigen binding proteins (MSAPs), such as trispecific antigen binding proteins (TSAPs or trispecific T cell engagers), that specifically bind to CD20, CD19, and CD3. Also provided are TSAPs or bispecific antigen binding proteins (BSAPs), that specifically bind to CD3 and CD20. Compositions (e.g., pharmaceutical compositions), kits, methods of use (e.g., treating cancer), and methods of making thereof are also provided.

The present invention relates to the treatment of subjects having CD20-positive cell proliferative disorders (e.g., B cell proliferative disorders, such as non-Hodgkin's lymphomas). More specifically, the invention pertains to the treatment of subjects having a B cell proliferative disorder by intravenous administration of an anti-CD20 / anti-CD3 bispecific antibody (e.g., mosunetuzumab).