45 results about "Bifunctional Antibodies" patented technology

Belonging to the field of tumor treatment and molecular immunology, the invention relates to an anti-CTLA4-anti-PD-1 bifunctional antibody, a pharmaceutical composition and use thereof. Specifically, the anti-CTLA4-anti-PD-1 bifunctional antibody comprises: a PD-1 (programmed death-1) targeted first protein functional region, and a CTLA4 (cytotoxic T lymphocyte sociated antigen 4) targeted second protein functional region. The bifunctional antibody provided by the invention can well bind to CTLA4 and PD-1 specifically, specifically remove the immunosuppression of CTLA4 and PD-1 on the body, and activate T lymphocytes, thus having good application prospect.

The invention discloses a VEGF-resistant and PD-1-resistant difunctional antibody and application thereof, belonging to the technical field of molecular immunology. The VEGF-resistant and PD-1-resistant difunctional antibody contains a light chain an a heavy chain, wherein the light chain has an amino acid sequence as shown in SEQ ID NO.2, and the heavy chain has an amino acid sequence as shown in SEQ ID NO.4 or SEQ ID NO.6. Meanwhile, the invention provides a gene for encoding the difunctional antibody and the application of the difunctional antibody. The difunctional antibody provided by the invention can be combined with PD-1 and VEGF, has very high affinity, can be used for effectively simulating T cells to secrete IL2 and induce T cells to secrete IFN-gamma and can also be used for remarkably inhibiting the growth of tumor of a mouse so as to have a huge potential in application to preparation of anti-cancer drugs.

The present invention relates to methods for separating cells using immunorosettes. The method involves contacting a sample containing nucleated cells and red blood cells with an antibody composition which allows immunorosettes of the nucleated cells and the red blood cells to form. The antibody composition preferably contains bifunctional antibodies or tetrameric antibody complexes.

The present invention relates to methods for separating cells using immunorosettes. The method involves contacting a sample containing nucleated cells and red blood cells with an antibody composition which allows immunorosettes of the nucleated cells and the red blood cells to form. The antibody composition preferably contains bifunctional antibodies or tetrameric antibody complexes.

The present invention provides methods of use of various antibody-immunostimulant fusion proteins as adjuvants of antigenic protein vaccinations to elicit humoral and / or cellular immune responses in vaccinated subjects. Compositions which include these fusion proteins and innate and / or exogenous antigenic proteins are also provided.

An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

The invention discloses a single-domain antibody combined with immune globulin, an anti-avian-influenza single-domain antibody, a bifunctional antibody and application thereof. The single-domain antibody capable of mediating and combining the immune globulin is screened from a constructed immune nano antibody gene library, the amino acid sequence of the single-domain antibody is shown as SEQ ID NO. 1-4, and the single-domain antibody can be specifically combined with human IgA, and the binding affinity with human IgG and mouse IgG is very low. The invention further provides the anti-avian-influenza single-domain antibody shown as SEQ ID NO. 5. The single-domain antibody is fused with other antibodies for tumors and viral pathogen antibodies or single-domain antibodies to construct a multifunctional specific fusion protein, and animal experiments prove that the constructed fusion protein has the effects of prolonging the half-life period of the functional antibody or the single-domain antibody in the body of an animal, effectively improving the bioavailability of the therapeutic antibody, remarkably enhancing the biological targeting treatment of the therapeutic antibody and the like.

The present invention relates to methods for separating cells using immunorosettes. The method involves contacting a sample containing nucleated cells and red blood cells with an antibody composition which allows immunorosettes of the nucleated cells and the red blood cells to form. The antibody composition preferably contains bifunctional antibodies or tetrameric antibody complexes.

The invention belongs to the field of tumor treatment and molecular immunology, and relates to an anti-CTLA4 and anti-PD1 bispecific antibody and application thereof. Specifically, the anti-CTLA4 andanti-PD1 bifunctional antibody comprises a first protein functional region targeting PD-1 and a second protein functional region targeting CTLA4, wherein according to an EU numbering system, a heavy chain constant region of immunoglobulin contained in the bispecific antibody mutates at any two or three of a 234th site, a 235th site and a 237th site, and after mutation, the affinity constant of thebispecific antibody and Fc[gamma]RIIIa and / or C1q is reduced compared with that before mutation. The bifunctional antibody disclosed by the invention can be well and specifically combined with CTLA4and PD-1, specifically relieves the immunosuppression of the CTLA4 and the PD-1 on the body, activates T lymphocytes and has a good application prospect.

The invention provides a novel bifunctional antibody conjugate, a preparation method and application thereof. The bifunctional antibody conjugate provided by the invention includes the structure of: a first antibody specifically directed at immune cells and a second antibody specifically directed at tumor markers, with the two antibodies coupled together through a coupling arm. The bifunctional antibody conjugate can significantly improve the tumor-killing activity after combination with an immune cell (like CIK). The invention also provides application of the novel bifunctional antibody conjugate in treatment of tumors and other diseases. The invention also provides an anti-HER2 positive cancer bispecific antibody and a preparation process. According to the invention, the bispecific antibody with high coupling rate and high activity can be simply and quickly produced, and the CIK tumor-killing activity can be improved by 2-6 times.

A bifunctional antibody has affinity for a target site and affinity for an organic molecule covalently linked to a cytotoxic agent or an enzyme capable of converting a prodrug into its cytotoxic form. The antibody may be used in therapy or diagnosis, especially in the treatment of tumours.

The invention provides an anti-PD-1 / EGFR bispecific antibody and an application thereof, and particularly provides the bifunctional antibody, which comprises: (a) an anti-EGFR antibody; and (b) an anti-PD-1 nanobody in a divalent form linked to the anti-EGFR antibody. The bifunctional antibody can be combined with EGFR and PD-1 at the same time, and therefore the treatment effect on EGFR positivetumor cells (especially malignant tumor cells) is achieved.

The invention relates to an anti-CD47 / CD20 bispecific antibody and an application thereof. Specifically, the invention provides the anti-CD47 / CD20 bispecific antibody, which comprises: (a) the anti-CD20 antibody (such as rituximab); and (b) the anti-CD47 nanobody in a monovalent form linked to the anti-CD20 antibody. The bifunctional antibody disclosed by the invention has good stability, the bifunctional antibody has the advantages that CD47 and CD20 can be specifically targeted, the interaction between CD47 and its ligand SIRPa is effectively blocked, CD20 on the cell surface is effectivelycombined, tumor cell proliferation can be remarkably inhibited, the synergistic effect of the bifunctional antibody is achieved, and the bifunctional antibody has a good application prospect.

The invention provides a method for effectively amplifying cytokine-induced killer (CIK) cells and improving specific tumor killing capability of the CIK cells. The method comprises the following steps: separating to obtain mononuclear cells; transferring the obtained mononuclear cells to a culture flask; adding CD3mAb with the final concentration of 400-600 ng / ml, CD28mAb with the final concentration of 1400-1600 ng / ml, IFN-gamma with the final concentration of 4000-4800 IU / ml and IL-2 with the final concentration of 4000-4800 IU / ml, IL-15 with the final concentration of 140-160 ng / ml; on the fourth day, replenishing fresh culture solution including 600-1000 IU / ml of IL-2 and 20-30 ng / ml of IL-15; on the sixth day, culturing the cells in separated flasks; on the eighth and ninth days, respectively transferring cells of the flask to a cell culture bag of 1.8 L, and replenishing fresh culture solution including 600-1000 IU / ml of IL-2 and 20-30 ng / ml of IL-15; at the eleventh day, culturing the cells in separated bags, and replenishing fresh culture solution including 600-1000 IU / ml of IL-2 and 20-30 ng / ml IL-15; continuously inducing and amplifying till the cells are obtained from the fifteenth day to the twenty-first day; incubating the obtained cells for 30-40 minutes at the room temperature by utilizing anti-EGFR and anti-CD3 bifunctional antibodies, washing the incubated cells in normal saline, and collecting the cells, thereby obtaining specific tumor-killing CIK cell preparations.

The invention provides a bifunctional antibody. The bifunctional antibody can be simultaneously combined with a human PD-1 antigen and an HER2 antigen, can effectively inhibit the combination of PD-1,HER2 and corresponding receptors, can specifically target T cells to HER2 high-expression tumor tissues, activates the T cells, and generates an anti-tumor effect. The bispecific antibody disclosed by the invention can be applied to treatment of HER2 positive tumors.

The invention relates to a stable CD3-CD19 resisting mini-type difunctional antibody of disulfide bond and a preparation method thereof. The preparation method comprises the steps of based on the CD3-CD19 resisting antibody, introducing amino acid Cys mutation in the CD3VL-resisting 100th amino acid Ser and CD3VH-resisting 44th amino acid Gly, wherein the expressed product has the structure of disulfide bond formed by the CD3VL-resisting 100th and the CD3VH-resisting 44th cysteines shown in the sequences 3 and 4. The stable CD3-CD19 resisting mini-type difunctional antibody of disulfide bond introduces cysteine mutation in the bits of VL-100 and VH-44 in the CD3-resisting variable region, and the disulfide bond is formed in a bacterium periplasm cavity between the variable region fragments of the two expressed single chains, i.e., between the CD3VL-CD19VH resisting segment and the CD19VL-CD3VH resisting segment, thereby enhancing the stability of the antibody; besides, a mutational site is located in a conservative framework region and two mutational sites in the space conformation are closer enough without generating tension so that the activity of the transformed difunctional antibody remains unchanged and the stability is enhanced.

The invention provides an antibody. The antibody comprises a protein dimer, wherein the protein dimer comprises a first functional domain including an immunoglobulin chain or an antibody combining site of a specifically-recognized specific antigen and a second functional domain including an immunoglobulin chain or an antibody combining site of a specifically-recognized specific antigen. The antibody is characterized in that the first functional domain consists of a first VH structural domain and a first VL structural domain, and the second functional domain consists of a second VH structural domain. The VH is a heavy chain variable zone, and the VL is a light chain variable zone. The bifunctional antibody provided by the invention has the advantages that a half-life period is greatly prolonged; and a homodimer is extremely less, so that identification and removal can be carried out only through primary purification even if aggregates occur.

The invention provides an anti-CD47 / VEGF bispecific antibody and an application thereof. The anti-CD47 / VEGF bispecific antibody comprises: (a) the anti-VEGF antibody bevacizumab; and (b) the anti-CD47monodomain antibody in a monovalent form linked to the anti-VEGF antibody. The bifunctional antibody disclosed by the invention not only can specifically target CD47 and VEGF and effectively block the interaction between a target and a ligand thereof, but also can effectively inhibit tumor cell proliferation, reserves the anti-tumor functions of a CD47 single-domain antibody and bevacizumab, andhas a good application prospect.

The invention relates to the technical field of antibodies, in particular to an anti-PD1 and TGF beta bifunctional antibody, a preparation method thereof and a pharmaceutical composition containing the same. The bifunctional antibody comprises a first protein functional region targeting PD-1 and a second protein functional region targeting TGF beta, the first protein functional region is a PD-1 antibody, and the second protein functional region is an extracellular structural domain of TGF beta RII; and an antibody heavy chain C end of the first protein functional area is connected with the N end of the second protein functional area.

The invention provides a bifunctional antibody and a construction method thereof. The bifunctional antibody comprises an antibody heavy chain constant area, an antibody light chain constant area, a first target protein, which is connected to the antibody heavy chain constant area, and a second target protein, which is connected to the antibody light chain constant area. The construction method of the bifunctional antibody comprises the following steps: individually obtaining the antibody heavy chain constant area gene, antibody light chain constant area gene, the first target gene, and the second target gene; adopting expression carriers to construct recombinant carrier shuttle plasmids of the genes mentioned above; transfecting the recombinant carrier shuttle plasmids to an expression bacterium strain to carry out culture so as to obtain the bifunctional antibody; carrying out centrifugation, and collecting the supernate or purifying the cells so as to obtain the bifunctional antibody. The construction method assembles antibody molecules in a gene level, thus the pertinence is strong, and the method is easy to achieve. The obtain bifunctional antibody comprises two antigen combining sites, so the bifunctional antibody can combine two different antigens at the same time.

The invention relates to an anti-HER2 / anti-PD-L1 bifunctional antibody and an application thereof. The anti-HER2 / anti-PD-L1 bifunctional antibody comprises: a monoclonal antibody unit, which aims at HER2 and comprises two heavy chains and two light chains; a single-chain antibody unit aims at PD-L1 and comprises two single-chain antibodies, each single-chain antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region and the light chain variable region are connected through a connecting peptide, and N ends or C ends of the two single-chain antibodies are respectively connected with C ends of Fc fragments of two heavy chains of the monoclonal antibody unit through linker. The anti-HER2 / anti-PD-L1 bifunctional antibody disclosed by the invention can be combined with PD-L1 and also can be combined with HER2, so that the anti-HER2 / anti-PD-L1 bifunctional antibody is a novel antitumor drug.

The invention relates to enzyme linked immunosorbent assay kits and in particular provides a bifunctional antibody serving as positive control in detection of hepatitis C virus. The bifunctional antibody is prepared from a mouse anti-HCV antibody and an anti-mouse IgG antibody by virtue of a chemical modification method. The bifunctional antibody prepared by utilizing an immunological method is taken as positive control of a hepatitis C indirect enzyme immunoassay diagnostic reagent, the source of the positive control material is solved, and the potential risk due to use of human serum is avoided.

The invention provides a bifunctional antibody for relieving immunosuppression in a tumor immune microenvironment as well as application and a preparation method of the bifunctional antibody. The bifunctional antibody is of a bifunctional scDb-CH3 structure with a stable disulfide bond formed by combining a PD-L1 antibody variable region and a TGF-[beta]s antibody variable region, and comprises the PD-L1 antibody variable region, the TGF-[beta]s antibody variable region, a hinge structural domain of human IgG 1 capable of generating the disulfide bond, a CH3 structural domain of human IgG1 and a connecting peptide. The bifunctional antibody provided by the invention is designed into a divalent form with a stable disulfide bond so as to enhance the affinity to a target spot, has a gene smaller than that of an IgG antibody, can block PD-L1 and TGF-beta signal channels at the same time, and can realize the effects of low dose and high drug effect; besides, the bifunctional antibody selects high-expression PD-L1 of tumors as a target spot, so that the bifunctional antibody has the effect of enriching in a tumor microenvironment in a targeted manner without blocking TGF-beta signals in a non-pathophysiological process, the targeting property and safety of drugs are improved, and more efficient and safe choices are provided for tumor treatment.

The invention discloses a separation method for plasma cells capable of secreting antigen specific antibodies. The plasma cells capable of secreting the antigen specific antibodies are obtained through separating a plasma cell marker CD38 or CD138 mono-antibody and anti-IgG antibody cross-linked double-functional antibody and a magnetic bead which is crossly linked with a specific antigen. By adopting the separation method, the plasma cells capable of secreting the antigen specific antibodies can be accurately obtained, the working amount is extremely reduced, and the success rate is higher.

The present disclosure relates to the development and use of an immunomodulator that is an antibody or antigen-binding portion thereof that binds to PD-L1. The PD-L1 antibody has high blocking activity on combination of PD-L1 and PD-1, a novel bifunctional antibody formed by the PD-L1 antibody and TGFBR2 can release the anti-tumor activity of T cells by blocking interaction of PD-L1 and PD-1, meanwhile, immunosuppression caused by activation of a smad signal channel by TGF-beta in a tumor microenvironment is effectively blocked, and the anti-tumor activity of the T cells is improved. The induction of effective and lasting anti-tumor immune response in the tumor which is not reacted originally is facilitated.

The invention relates to the technical field of antibodies, in particular to a bifunctional antibody for resisting PD-L1 and 4-1BB and medical application of the bifunctional antibody. The selected 4-1BB antibody needs to be supported by a cross-linking effect in the aspect of immunocompetence stimulation, the cross-linking effect is avoided, and the 4-1BB antibody has no activity, so that toxic and side effects on the liver are avoided. In a tumor environment, tumor cells have a relatively high PD-L1 expression level. According to the PD-L1 / 4-1BB bifunctional antibody, the PD-L1 antibody part is combined with PD-L1 on the surface of a tumor cell, so that a relatively strong cross-linking effect is provided for a 4-1BB antibody. Therefore, the immunostimulatory activity of the PD-L1 / 4-1BB bifunctional antibody can be specifically and remarkably improved in a tumor microenvironment, so that toxic and side effects of the 4-1BB antibody in the liver are avoided or reduced.

The invention provides a chicken IgY bifunctional antibody for treating helicobacter pylori, relates to the field of therapeutic bifunctional antibodies and relates to a chicken IgY antibody for treating helicobacter pylori and a modification method of the chicken IgY antibody. The invention aims at adopting a method of a bifunctional antibody to solve the problems of drug resistance of helicobacter pylori treatment medicines, long treatment period and radical treatment difficulty of an orally-taking IgY antibody and achieves the effect of antibiotic and anti-helicobacter pylori antibody bifunctional helicobacter pylori treatment by modifying a helicobacter pylori resistant chicken IgY antibody with multiple chemical substances and multiple different methods, so that the treatment period can be shortened, the drug resistance of the helicobacter pylori on antibiotics can be reduced, toxic and side effects of antibiotics can be reduced, and the treatment scheme on the helicobacter pylorican be optimized.

The invention relates to an anti-CD47 / CD20 bispecific antibody and an application thereof. Specifically, the invention provides the anti-CD47 / CD20 bispecific antibody, which comprises: (a) the anti-CD20 antibody (such as rituximab); and (b) the anti-CD47 nanobody in a monovalent form linked to the anti-CD20 antibody. The bifunctional antibody disclosed by the invention has good stability, the bifunctional antibody has the advantages that CD47 and CD20 can be specifically targeted, the interaction between CD47 and its ligand SIRPa is effectively blocked, CD20 on the cell surface is effectivelycombined, tumor cell proliferation can be remarkably inhibited, the synergistic effect of the bifunctional antibody is achieved, and the bifunctional antibody has a good application prospect.

The invention aims at providing a novel antibody drug conjugate and a preparation method of an Ig gamma antibody-coupled broad-spectrum anticancer drug. Intestinal cancer cells are taken as an immunogen to immunize poultry to obtain an Ig gamma antibody aiming at the intestinal cancer, and a chicken Ig gamma antibody for resisting the intestinal cancer is modified by a plurality of chemotherapeutic drugs and a plurality of different methods, so that a preparation method of an orally-taken bifunctional antibody is provided. After the novel antibody drug conjugate is orally taken, the novel antibody drug conjugate can be combined with the intestinal cancer, and has cytotoxicity for resisting the intestinal cancer, and the drug resistance and toxic and side effects of the chemotherapeutic drugs are reduced.