Structure of mesothelin and therapeutic antibody complex
نویسندگان
چکیده
Background: Mesothelin is a tumor differentiation antigen; its binding to tumor-antigen CA-125 can lead to tumor metastasis. Results: Structures of the Fab from a therapeutic antibody MORAb-009 and its complex with an epitope-containing fragment of mesothelin are obtained. Conclusion: Overlapping binding sites for both CA-125 and MORAb-009 provides a basis for the antibody’s therapeutic effect. Significance: This work represents the first structure for mesothelin.
منابع مشابه
Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors
ABSTRACT BACKGROUND Monoclonal antibodies have become attractive clinical anti-cancer drugs in the last 3 decades due to their targeting specificity and suitable pharmacokinetic properties. Mesothelin is a tumor-associated antigen with limited expression in normal tissues. It is frequently over-expressed on the cell membrane of a number of epithelial malignancies (e.g. mesothelioma, pancreatic,...
متن کاملA human single-domain antibody elicits potent antitumor activity by targeting an epitope in mesothelin close to the cancer cell surface.
Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma and multiple forms of cancers, and show great promise for clinical development for solid cancers. Antibodies against mesothelin have been shown to act via immunotoxin-based inhibition of tumor growth and induction of antibody-dependent cell-mediated cytotoxicity (ADCC). However, complement-dependent c...
متن کاملAnetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect.
Mesothelin is a tumor differentiation antigen frequently overexpressed in tumors such as mesothelioma, ovarian, pancreatic, and lung adenocarcinomas while showing limited expression in nonmalignant tissues. Mesothelin is therefore an attractive target for cancer therapy using antibody-drug conjugates (ADC). This study describes the detailed characterization of anetumab ravtansine, here referred...
متن کاملNear infrared photoimmunotherapy with an anti-mesothelin antibody
Near Infrared-Photoimmunotherapy (NIR-PIT) is a new, highly selective tumor treatment that employs an antibody-photon absorber conjugate (APC). When the APC attaches to its target cell and is exposed to NIR light, highly selective cell killing is observed. NIR-PIT has been demonstrated with a limited number of antibodies. Mesothelin is overexpressed in several malignancies and is emerging as a ...
متن کاملA novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity.
Mesothelin is a potential new target for cancer immunotherapy because it is present at relatively low levels only in mesothelial cells of pleura, peritoneum, and pericardium of healthy people, but is significantly elevated in a number of tumors, including mesothelioma, ovarian, pancreatic, and lung cancers. However, all currently available antibodies against mesothelin are either murine or chim...
متن کامل