Bispecific antibodies.

Bispecific antibodies--molecules combining two different antigenic specificities--are currently being developed as new agents for immunotherapy and for basic studies in cell biology. Bispecific antibodies (BsAb) are prepared by chemically linking two different monoclonal antibodies or by fusing two hybridoma cell lines to produce a hybrid-hybridoma. Both of these approaches present challenges with respect to yield and purity that should eventually be solved through newer molecular genetic approaches. BsAb have been used to demonstrate that specific surface molecules can trigger leukocytes to either phagocytose or kill tumor cells, viruses, parasites, and infected cells. Such trigger molecules include CD3 on T lymphocytes and Fc receptors for IgG on monocytes, macrophages, and natural killer cells. BsAb have also been used experimentally to localize toxins to tumor sites and fibrinolytic agents to areas of thrombosis, to study the molecular specificity of particular receptors, and as adjuvants in in vitro models of vaccines for infectious disease. The limited clinical trials that have occurred to date, primarily for therapy of tumors, suggest that BsAb may offer considerable promise for therapeutic applications, including cancer, heart disease, infectious disease, allergy, and autoimmunity.