Bispecific antibody treatment of murine B cell lymphoma.
This report summarizes our experimental data concerning the use of bispecific antibodies (bsAb) for the treatment of the murine BCL1 B cell lymphoma model. Initially we used a hybrid-hybridoma-derived bsAb with specificity for the TcR/CD3 complex on T cells and the idiotype of the membrane-bound IgM on the tumor cells. The bsAb used as a single agent could cure animals with a low tumor load (resembling minimal residual disease). However, in experiments aimed at increasing the therapeutic effect in animals with a higher tumor burden, we could demonstrate the importance of additional T-cell-costimulatory signals and the careful timing of the bsAb administration. Recently we have generated a bispecific single-chain Fv (bsscFv) fusion protein with the same dual specificity as the hybrid-hybridoma-derived bsAb. Immunotherapy with this smaller molecule also resulted in tumor elimination in BCL1-bearing mice. A second bsscFv (alpha-CD19 x alpha-CD3) with a broader applicability is now being characterized and tested in vivo.
De Jonge
J
J
Laboratory of Physiology, Medical School, Vrije Universiteit Brussel, (VUB), Belgium.
Heirman
C
C
De Veerman
M
M
Van Meirvenne
S
S
Demanet
C
C
Brissinck
J
J
Thielemens
K
K
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000954:Antigens, Surface; D017252:CD3 Complex; D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M