title: Anti-CD3:anti-IL-2 receptor bispecific monoclonal antibody. Targeting of activated T cells in vitro.
abstract: T cells are major mediators of graft rejection and many autoimmune diseases. During the Ag recognition process, T cells often become activated. We tested the hypothesis that an anti-CD3:anti-CD25 (CD3,25) bispecific mAb (BSMAB) can effectively and selectively target activated T cells. By flow cytometric analysis, the CD3,25 BSMAB was shown to bind avidly to activated T cells that coexpress CD3 and CD25 (p55 chain of the IL-2R), achieving higher levels than the parent anti-CD3 and anti-CD25 mAb. It bound only weakly to unstimulated T cells. The CD3,25 BSMAB effectively redirected CTL to lyse CD25-bearing PHA-stimulated T lymphoblasts and the IL2-dependent CTLL tumor cell line in chromium release assays. It was highly effective in blocking MLR as shown by inhibition of [3H]TdR incorporation. However, the CD3,25 BSMAB has a low potential to activate resting T cells, as it induced only minimal [3H]TdR incorporation even in the presence of exogenous IL-2. In the absence of exogenous IL-2, the CD3,25 BSMAB was unable to induce [3H]TdR incorporation. In contrast, the parent anti-CD3 mAb induced a high degree of incorporation. In summary, the CD3,25 BSMAB selectively targets activated CD25-expressing T cells and lymphomas although maintaining a low activation potential for unstimulated T cells, potentially advantageous properties that can be exploited for immunotherapy.
authors.affiliation: Department of Pathology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
authors.forename: J A
authors.initials: JA
authors.lastname: MacLean
authors.forename: Z
authors.initials: Z
authors.lastname: Su
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: M S
authors.initials: MS
authors.lastname: Sy
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: J T
authors.initials: JT
authors.lastname: Wong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001667:Binding, Competitive; D017252:CD3 Complex / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006822:Hybrid Cells; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins