Monoclonal antibodies in urologic oncology
The sensitivity and specificity of immune reactions have long been recognized. However, since the description of the monoclonal antibody technique certain technical hurdles have been overcome. Monoclonal antibody (mAb) technology allows far more precise understanding of the humoral immune response by allowing dissection of this response into its individual B-lymphocyte populations. Furthermore, the ability to select and expand a particular B-cell clone allows for production of unlimited amounts of a pure antibody "reagent." Each of these reagents may be readily used as a "probe" for its respective antigenic determinant. Panels of these reagents may be used to probe complex biologic structures (e.g., neoplastic cells) and thereby "dissect" them at a molecular level. Murine mAbs are produced by hyperimmunizing a mouse with the antigen of interest. The spleen provides a rich source of B-lymphocytes. These normal B-lymphocytes are incapable of surviving in culture. However, mouse B-lymphocyte tumor cell lines (myelomas) have been previously immortalized in tissue culture. A hybridoma is formed by fusing the normal immunized B-cells with myeloma cells. The hybridoma combines the best features of its parent cells. The immunoglobulin product of each resulting clone is screened against a panel of antigens. This allows selection of those clones producing antibody to the desired antigens. The mAb may be used to purify and/or characterize its respective antigen including definition of the chromosomal site of its gene and factors involved in the regulation of its expression. A large number of mAbs have been produced against renal, bladder, and prostate cancer antigens. These mAbs are allowing a more precise, molecular subclassification of these cancers and providing improved predictability of the natural history of each patient's cancer. Evidence in experimental animals demonstrates that mAbs accumulate at the site of tumor and can lead to the destruction of tumor cells. These encouraging results have prompted clinical trials in patients with metastatic cancer. Such a clinical trial in patients with metastatic renal cancer is currently underway at New York Hospital and Memorial Sloan-Kettering Cancer Center.