Idiotype-specific inhibition of LFA-1-mediated cell adhesion by anti-idiotype×anti-LFA-1 bispecific antibodies

Abstract

Adhesion molecules are involved in lymphoma dissemination. Antibodies to adhesion molecules may block tumor metastasis. However, such antibody treatment may block as well normal functions of the immune system. We tested the hypothesis that a bispecific antibody with specificity for an adhesion molecule and for a tumor specific antigen binds preferentially to tumor cells which coexpress both antigens and hence selectively blocks adhesion. A bispecific antibody was developed by somatic cell hybridization of two hybridomas, one producing a monoclonal antibody against the immunoglobulin idiotypic determinant of the murine B cell lymphoma 38C-13 and the other producing an antibody against the α subunit (CD11a) of the adhesion molecule LFA-1. The bispecific antibody, anti-idiotype×anti-LFA-1, was purified by affinity chromatography. The dual specificity of the hybrid hybridoma product was demonstrated by a radioimmunoassay devised for detection of bifunctional activity. The bispecific antibody was shown by flow cytometry to bind efficiently to 38C-13 cells that coexpress idiotype and LFA-1. It bound only weakly to idiotype-negative variants of 38C-13 that express only LFA-1. In binding assays to immobilized ICAM-1, the anti-idiotype×anti-LFA-1 was highly active in blocking 38C-13 cell adhesion. However, it did not effect adhesion of idiotype-negative tumor cells or of normal T lymphocytes. In summary, the bispecific antibody preferentially blocks adhesion of cells that coexpress the tumor specific antigen and the adhesion receptor. The present approach may provide a general way for the selective adhesion blockade of a specific cell population.