Monoclonal Antibodies as Anticancer Agents

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Abstract

A major problem with current modalities of cancer treatment has been the lack of specificity of the treatment for the cancer cell. It is well known that the therapeutic/toxic ratio is low for anticancer drugs and for radiation therapy. A major advance in the treatment of cancer could be heralded by the development of a class of agents that have a greater degree of specificity for the tumor cell. The technique of hybridization of an immortal myeloma cell line with an antibody-producing B cell as developed by Kohler and Milstein in the late 1970’s provided a technique by which monoclonal antibodies could be produced in virtually unlimited quantities (1). Since the technique involved the selection of single cells and the clonal expansion of a single hybrid between the antibody-forming cell and the myeloma cell, this technique makes available, for the first time, monoclonal antibodies for use in cancer biology. Since most of the monoclonal antibodies developed against human tumor cells have been made in mice by immunizing the mouse with human tumor cells or extracts thereof, these monoclonals are mouse immunoglobulins and represent the way a mouse cell sees a human tumor cell. While there are many difficulties with respect to using mouse immunoglobulins as therapeutic reagents in man, this technique may provide one route around the problem of immunogenicity of tumors in man. It is possible that the mouse will recognize antigenic determinants on the human tumor cell not recognized by the patient’s own immune system or not recognized well by that immune system. If this turns out to be the case, we will have a mechanism for developing specific monoclonal reagents defining antigenic specificities on the tumor cell which may be unique and cancer specific though nonimmunogenic in the primary host. Therefore, investigations into mouse monoclonal antibody may be important even given the future availability of human-derived monoclonal antibodies and even with the potential toxicities of mouse immunoglobulin reagents.