Human monoclonal antibodies to prostate specific membrane antigen and a transgenic mouse to produce the antibody

摘要

An isolated human monoclonal antibody specifically binds to prostate-specific membrane antigen (PSMA) with an affinity constant of at least about 107M-1. The antibody binds to native human PSMA but not to heat denatured human PSMA, mediates antibody dependant cellular cytotoxicity (ADCC) and is internalized by PSMA-expressing cells. An isolated human monoclonal antibody which specifically binds to human PSMA and mediates cytolysis or inhibits growth of cells expressing human PSMA in the presence of human effector cells and a hybridoma comprising a B cell obtained from a transgenic non-human animal having a genome comprising a human heavy chain transgene and a light chain transgene, fused to a an immortalized cell which produces the antibodies are described. Also described are a method of producing an antibody, bispecific and multispecific molecules comprising the antibodies, methods for detecting the presence of PSMA antigen or a cell expressing PSMA and a nucleic acid encoding the variable region of the antibody. The antibodies can be used in the production of a composition for inhibiting growth of a cell expressing PSMA, for inducing cytolysis of a cell expressing PSMA in the presence of a effector cell and for the treatment or prevention of a disease characterized by aberrant expression of PSMA, preferably the disease is cancer.