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Syngeneic Anti-idiotype Monoclonal Antibodies to Murine Anticarcinoembryonic Antigen Monoclonal Antibodies¹

Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103

BALB/c mice were immunized with either NP-3 or NP-4, two anticarcinoembryonic antigen murine monoclonal antibodies. Each animal produced anti-idiotype antibodies to the corresponding immunogen and no cross-reactivity between anti-NP-3 sera and anti-NP-4 sera was detected. Hybridomas were produced from these animals and two IgG₁ anti-idiotype monoclonal antibodies were obtained: CM1 specific for NP-3 and CM11 specific for NP-4. CM1 and CM11 recognized determinants located within the antibody-combining site, since each anti-idiotype antibody inhibited the binding between the corresponding idiotype and carcinoembryonic antigens. Using an immunoblotting technique, neither CM1 nor CM11 reacted with isolated heavy or light chains of NP-3 or NP-4, whereas binding was observed with the intact molecule. This observation indicates that CM1 and CM11 are directed against conformational idiotypes resulting from the association of the variable regions of the heavy and light chains. Taken together, these results suggest that CM1 and CM11 might bear internal images of carcinoembryonic antigen epitopes, and that they are potential candidates as idiotype vaccines against colorectal tumors.

¹ Supported in part by NIH Grant CA 39841.

² To whom requests for reprints should be addressed, at the Center for Molecular Medicine and Immunology, 1 Bruce Street, Newark, NJ 07103.

Received 6/21/88. Revised 9/21/88. Accepted 9/30/88.