IDIOTYPE-SPECIFIC INHIBITION OF LFA-1-MEDIATED CELL-ADHESION BY ANTIIDIOTYPE X ANTI-LFA-1 BISPECIFIC ANTIBODIES

Adhesion molecules are involved in lymphoma dissemination. Antibodies to adhesion molecules may block tumor metastasis. However, such antibo dy treatment may block as well normal functions of the immune system. We tested the hypothesis that a bispecific antibody with specificity f or an adhesion molecule and for a tumor specific antigen binds prefere ntially to tumor cells which coexpress both antigens and hence selecti vely blocks adhesion. A bispecific antibody was developed by somatic c ell hybridization of two hybridomas, one producing a monoclonal antibo dy against the immunoglobulin idiotypic determinant of the murine B ce ll lymphoma 38C-13 and the other producing an antibody against the a s ubunit (CD11a) of the adhesion molecule LFA-1. The bispecific antibody , anti-idiotype x anti-LFA-l, 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 efficient ly to 38C-13 cells that coexpress idiotype and LFA-1. It bound only we akly to idiotype-negative variants of 38C-13 that express only LFA-1. In binding assays to immobilized ICAM-1, the anti-idiotype x anti-LFA- l was highly active in blocking 38C-13 cell adhesion. However, it did not effect adhesion of idiotype-negative tumor cells or of normal T ly mphocytes. In summary, the bispecific antibody preferentially blocks a dhesion of cells that coexpress the tumor specific antigen and the adh esion receptor. The present approach may provide a general way for the selective adhesion blockade of a specific cell population. (C) 1998 E lsevier Science B.V. All rights reserved.