Humanized and chimeric anti-TROP-2 antibodies that mediate cancer cell cytotoxicity

A technology of humanized antibody and cytotoxicity, which is applied in the field of diagnosis and treatment of cancer diseases, and can solve problems such as unknown antibodies
CN101679526AInactive Publication Date: 2010-03-24F HOFFMANN LA ROCHE & CO AG
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
F HOFFMANN LA ROCHE & CO AG
Publication Date
2010-03-24
Estimated Expiration
Not applicable · inactive patent

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Abstract

Expression of TROP-2, an approximately 35 kDa transmembrane protein and a substrate of protein kinase C, has been linked to several cancers. TROP-2 is also known as GA733-1, epithelial glycoprotein 1(EGP-I) and tumor-associated calcium signal transducer-2. A monoclonal antibody against TROP-2 from the hybridoma AR47A6.4.2, deposited with the International Depository Authority of Canada (IDAC) asaccession number 141205-05, was previously shown to be a cancerous disease modifying antibody (CDMAB), preventing tumour growth and reducing tumour burden in several cancer models including prostate,pancreatic and breast cancer by cytotoxicity. The variable regions of this monoclonal antibody were also isolated, sequenced and complementarity determining regions (CDRs) determined. Now, a chimericantibody and humanized antibodies are generated that have similar TROP-2 binding activity as the parent 141205-05 monoclonal antibody. The monoclonal, chimeric and humanized antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells to treat cancer. These antibodies are also used in binding assays to determineTROP-2 expression on cells.
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Description

field of invention

[0001] The present invention relates to the diagnosis and treatment of cancerous disease, in particular, to mediating tumor cell cytotoxicity; and, more particularly, to antibodies (CDMAB) that ameliorate cancerous disease, optionally in combination with one or more CDMAB / chemotherapy agents Application as a tool for initiating a cytotoxic response. The invention also relates to binding assays utilizing the CDMABs of the invention. Background of the invention

[0002] TROP-2 is a cell surface glycoprotein expressed on most cancers, as well as some normal human tissues. It was originally defined as the molecule recognized by two murine monoclonal antibodies raised against the human choriocarcinoma cell line BeWo, which recognizes an antigen on human trophoblast cells (Faulk 1978). Other investigators independently discovered the same molecule, leading to multiple names describing the same antigen. Therefore, TROP-2 is also known as GA733-1 and epithelial...

Claims

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