60 results about "Complement-dependent cytotoxicity" patented technology

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38⁺ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

The present invention relates to methods for selecting, obtaining or producing Fc variant polypeptides which show altered recognition for an Fc ligand (e.g., FcγR, CIq). Additionally, the Fc variant polypeptides may have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variant polypeptides particularly for therapeutic purposes.

Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and/or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.

The present invention relates to novel Fc variants of antibodies that immunospecifically binds to Integrin α_vβ₃. The Fc variants comprise a variable region that immunospecifically binds to Integrin α_vβ₃ and a Fc region that further comprises at least one novel amino acid residue which may provide for enhanced effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants of an antibody that immunospecifically binds to Integrin α_vβ₃, particularly for therapeutic purposes.

The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or CIq. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

The present disclosure concerns an antibody that specifically binds CD38 which is capable of killing a CD38⁺ cell by induction of apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity. The disclosed antibody may be used as a medicament or in the making of a medicament, wherein the antibody is to be administered to a human subject in a safe therapeutic dose of about 20 mg/kg or below. In one embodiment, the medicament is for treating CD38+ multiple Myeloma in humans.

The invention discloses an anti-human CLDN18.2 antibody as well as an antigen binding fragment and a medical application thereof. Specifically, the present invention relates to a murine antibody comprising a CDR region of the anti-human CLDN18.2 antibody, a chimeric antibody and a humanized antibody, a fully humanized antibody, an antibody-dependent cytotoxicity (ADCC) comprising the antibody andthe antigen binding fragment thereof, complement dependent cytotoxicity (CDC), the killing effect on CLDN18.2 positive cells, the effect of inhibiting the growth of CLDN18.2 positive tumors, the in-vivo drug effect, a medicine containing the anti-human CLDN18.2 antibody and the antigen binding fragment thereof, a composition of the medicine thereof, and an application of the medicine in tumor treatment, in particular to treatment of CLDN18.2 positive tumor patients..

Engineered lectins and methods of using such reagents for both preventing and treating a broad array of viral infections are provided. The lectins of the invention are engineered in two ways, first through the enhancement of the natural mode of action of lectins against viruses through linked multimerization, and second through the creation of a new class of reagents, hereinafter referred to as a “lectibody” or “lectibodies”, that engage host immune function in addition to simply binding glycosylated viral proteins via the combination of a lectin and the Fc region of an antibody in order to drive Fc-mediated effector functions including ADCC (antibody-dependent cell-mediated cytotoxicity), increased half-life, complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated phagocytosis (ADCP) in response to a lectin-mediated carbohydrate-binding event.

A variant of a polypeptide comprising a human IgG Fc region is described, which variant comprises an amino acid substitution at one or more of amino acid positions 270, 322, 326, 327, 329, 331, 333 or 334 of the human IgG Fc region. Such variants display altered effector function. For example, C1q binding and/or complement dependent cytotoxicity (CDC) activity may be altered in the variant polypeptide. The application also discloses a variant of a parent polypeptide comprising a human IgG Fc region, which variant has a better binding affinity for human C1q than the parent polypeptide

The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab')2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab')2-LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which improves stability and/or alters the binding of Fc to one or more metal ion and/or one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that are less susceptible to metal ion-mediated cleavage and/or have modified binding affinity to one or more FcγR and/or C1q. Additionally, the Fc variants have altered antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. Furthermore, the modified hinge of the Fc variants retains a similar flexibility to the wild type hinge. The invention further provides methods and protocols for the application of said Fc variants particularly for therapeutic purposes.

According to the complement-dependent cytotoxicity (CDC) reaction principle in the immunology said invention creates an in-vitro enzyme-linked immunoreactino method for assaying HLA complement fixingantibodies (CFAbs) and its kit. The reaction system is formed from solid-phase HLA antigen or target cell with HLA antigen and liquid-phase enzyme-labelled ligand. CFAbs in the tested sample and solid-phase HLA antigen or HLA antigen of target cell are combined, and simultaneously fixed and existed in enzyme-labelled complement or the enzyme-labelled complement anti body is combined with complement fixed in HLA antigen-CFAb composite, then the correspondent enzyme substrate can be added to produce zymolygical color development reaction.

The present invention relates to methods and compositions for use in inducing tumor-specific antibody mediated complement-dependent cytotoxic response in an animal having a tumor comprising administering to said animal a composition comprising a replication competent oncolytic virus wherein administration of the composition induces in the animal production of antibodies that mediate a CDC response specific to said tumor.

Disclosed is a cholangiocarcinoma cell growth inhibitor comprising an anti-glypican-3 antibody as an active ingredient. Preferably, the anti-glypican-3 antibody has a cytotoxic activity such as an antibody-dependent cytotoxic (ADCC) activity and a complement-dependent cytotoxic (CDC) activity. Also disclosed is a diagnostic agent for diagnosis of cholangiocarcinoma comprising an anti-glypican-3 antibody.

The present invention describes the generation of an anti-idiotype single-chain Fv (scFv) antibody specific for the murine (RFB4), chimeric (SM03) and humanized (SM06) versions of an anti-CD22 antibody (the anti-CD22 antibodies). The present invention further describes the construction of a murine IgG2a/kappa immunoglobulin carrying the variable region sequences of the anti-idiotype scFv sequences. Additionally, the present invention provides a cell line capable of producing an anti-idiotype murine antibody specific for the anti-CD22 antibodies. The present invention is directed against a method for identifying and evaluating the activities and concentration of the anti-CD22 antibodies. Additionally, the present invention provides a method for evaluating serum concentration of the anti-CD22 antibodies that are being used clinically. The present invention is also directed against a method to detect HAMA, HACA and HAHA responses in patients treated with the anti-CD22 antibodies. Specifically, the present invention is directed against the establishment of a cell line expressing surface concentration of the antibody of the invention; the said cell line expressing surface anti-idiotype antibodies or antibody fragments will be used as the target cell line for evaluating the functional activities of the anti-CD22 antibodies via complement dependent cytotoxicity (CDC) and/or antibody dependent cell cytotoxicity (ADCC) activities.

The invention discloses a colorectal cancer stem cell vaccine preparation method and application. Postoperative tumor tissue cells derived from patients with colorectal cancer, human colorectal cancer cell lines Lovo or mouse colorectal cancer cell lines CT26 are prepared into CD133+ colorectal cancer stem cell vaccines by a repeated freezing-thawing method. The CD133+ colorectal cancer stem cell vaccines can reduce immunized mouse serum TGF-beta level, IFN-gamma level is improved, killing activity of NK (natural killer) cells and CDC (complement-dependent cytotoxicity) activity are enhanced, immunized mice resist colorectal cancer cell attack, immune cells are induced to selectively kill CD133+ colorectal cancer stem cells, and further tumor growth is inhibited.

The present invention discloses an antibody capable of binding to the PRG-3 protein and inhibiting the growth of cells expressing the PRG-3 protein. The growth inhibitory activity is cytotoxic activity, such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The present invention also discloses a pharmaceutical composition, cell growth inhibitor, and an anticancer agent comprising the antibody of the present invention as an active ingredient. Examples of the type of cancer include hepatocellular carcinoma, lung cancer, colon cancer, and glioblastoma. In addition, the present invention discloses a method for diagnosing cancer by detecting expression of the PRG-3 protein or the gene encoding the PRG-3 protein, as well as a diagnostic agent and kit for use in the method.

The invention relates to a recombinant human IL (Interleukin)-23 receptor extracellular region/Fc fusion protein capable of combining with IL-23 and antagonizing a function of IL-23. The fusion protein is characterized in that a fusion protein encoding gene is rich in mammalian cell preferred codons, and is highly expressed by a CHO (Chinese Hamster Ovary) stable transfection cell strain. The protein is formed by fusion of a gene optimized IL-23R-CHR active fragment and a human immune globulin molecule Fc fragment; the defects that the half-life period of the prokaryotic expression IL-23R-CHR fragment is short, the stability is poor and endotoxin is difficult to remove are overcome; the biological activity of IL-23-CHR is reserved; in addition, the fusion protein does not have ADCC (Antibody Dependent Cellular Cytotoxicity) and CDC (Complement Dependent Cytotoxicity) effects, so that the fusion protein is more suitable for treatment of chronic diseases such as an autoimmune disease and a chronic infection; and the contents of molecular design, expression, purification, construction of a stable expression cell strain and disease treatment and the like of the fusion protein are included.