Immunological and molecular characterization of an idiotypic cascade specific for the human carcinoembryonic antigen

Abstract

This chapter presents a study that focuses on the immunological and molecular characterization of an idiotypic cascade specific for the human carciniembryonic antigen (CEA). CEA is a class III tumor-associated antigens (TAA) of human solid tumors. It is widely used for in vitro diagnostic procedures and has proven to be suitable for in vivo tumor targeting approaches with CEA-specific monoclonal antibodies (mAbs). Knowledge of the expression pattern and detailed characterization of the antigens of the CEA family is expected to be important for generation of CEA-specific antibodies, their respective appropriate Ab2β antibodies, and characterization of immune responses elicited by the application of both types of immunoglobulins in vivo. In the given study, a nonrepetitive determinant defined by the murine mAb T84.66, an antibody with high affinity and CEA specificity, was chosen as the epitope for the generation of a CEA-specific idiotype cascade. Over a period of approximately 4 months, five immunizations were carried out in Balb/c mice using F(ab′)2 preparations of T84.66 coupled to KLH and adjuvans. Hybridiomas were selected and were subsequently tested for binding to T84.66 F(ab′)2 fragments. The study identified an anti-Id antibody 6G6.C4 as a promising candidate vaccine for eliciting an immune response against a TAA-specific epitope of the human CEA.