Antibodies that bind GalNAc1-3Gal, pharmaceutical compositions and methods of using same
Inventors
Gildersleeve, Jeffrey • Li, Zhitao • Li, Qian • Anver, Miriam • Butcher, Donna O.
Assignees
US Department of Health and Human Services
Publication Number
US-8957188-B2
Publication Date
2015-02-17
Expiration Date
2030-04-01
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Abstract
Monoclonal antibodies to carbohydrate antigens containing a terminal GalNAcα1-3Gal are provided. The antibodies of the present invention are found to specifically recognize GalNAcα1-3Gal with little cross-reactivity to other structurally similar antigens such as GalNAcα1-6Gal, blood group A, Forssman antigen and the Tn antigen on both solution assays and human tissue. Compositions comprising the monoclonal antibodies, as well as methods of diagnosis, treatment and prognostication are also provided.
Core Innovation
The invention provides monoclonal antibodies, or binding fragments thereof, which bind specifically to the carbohydrate antigen GalNAcα1-3Gal. These antibodies exhibit high specificity with little cross-reactivity to structurally similar antigens such as GalNAcα1-6Gal, blood group A, the Forssman antigen, and the Tn antigen. The antibodies can be labeled with detectable moieties or bound to solid matrices, and can be used in pharmaceutical compositions for diagnosis, treatment, and prognostication of cancer.
The problem addressed arises from major changes in carbohydrate expression during cancer progression, including loss of normal cell surface carbohydrates and increased expression of tumor-associated carbohydrate antigens. Current methods for detection of the Tn antigen in cancers are inconclusive due to antibodies cross-reacting with similar antigens, limiting accurate diagnosis and prognostication. Therefore, a need exists for antibodies that specifically recognize the GalNAcα1-3Gal antigen with minimal cross-reactivity to enable more precise cancer diagnostics and therapeutics.
Claims Coverage
The patent sets forth three independent claims covering the antibody itself, the hybridoma cell line producing the antibody, and labeled forms of the antibody. Key inventive features relate to specific binding to GalNAcα1-3Gal and exclusion of cross-reactivity to related antigens, along with pharmaceutical compositions and detection methods.
Monoclonal antibody specifically binding GalNAcα1-3Gal without cross-reactivity
A monoclonal antibody or binding fragment that binds specifically to GalNAcα1-3Gal expressed on the surface of cancer cells and does not bind to one or more of blood group A, Tn antigen, GalNAcα1-6Gal, and Forssman antigen.
Hybridoma cell line producing specific monoclonal antibody
A hybridoma cell line which produces a monoclonal antibody specifically binding to GalNAcα1-3Gal on cancer cells without binding to blood group A, Tn antigen, GalNAcα1-6Gal, and Forssman antigen.
Labeled monoclonal antibody with detectable moiety
The monoclonal antibody or binding fragment labeled with detectable moieties such as fluorophores, chromophores, radionuclides, chemiluminescent agents, bioluminescent agents, or enzymes.
Monoclonal antibody bound to solid matrix
The monoclonal antibody or binding fragment bound to a solid matrix to facilitate diagnostic or preparative uses.
Pharmaceutical composition comprising the monoclonal antibody
Compositions comprising the monoclonal antibody or binding fragment with pharmaceutically acceptable carriers, excipients, or diluents, optionally including therapeutic agents such as drugs, radioisotopes, immunomodulators, lectins, toxins, or combinations thereof.
The claims collectively cover the antibody specific to GalNAcα1-3Gal without cross-reactivity, the cell lines producing it, labeled and matrix-bound forms, and pharmaceutical compositions incorporating the antibody for cancer diagnostic and therapeutic applications.
Stated Advantages
The antibodies specifically recognize GalNAcα1-3Gal with minimal cross-reactivity, enabling accurate cancer diagnostics.
Monoclonal antibodies can be used as biochemical markers for prognosticating survival in various cancers such as cervical and laryngeal cancer.
The antibodies enable methods for detection, treatment, radioimaging, and survival prediction of cancers, improving clinical decisions.
Pharmaceutical compositions with these antibodies allow targeted therapy potentially reducing off-target effects.
Documented Applications
Diagnostic detection of cancer or precancer by detecting GalNAcα1-3Gal in biological samples.
Prognostication of patient survival in cancers including cervical and laryngeal carcinomas by assessing antigen expression levels.
Therapeutic treatment of cancer by administering pharmaceutical compositions comprising the specific monoclonal antibodies or their fragments.
Radioimaging of cancer cells or tumors by administering radioisotope-labeled monoclonal antibodies and detecting emitted radiation.
In vitro diagnostic applications including immunohistochemical staining, serological assays, and immunoassays for detection of cancer-associated GalNAcα1-3Gal antigen.
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