Potentiation of lysis of leukaemia cells by a bispecific antibody to CD33 and CD16 (Fc gamma RIII) expressed by human natural killer (NK) cells.
Bispecific antibodies recognizing tumour-associated antigens and trigger molecules expressed on immune effector cells have been shown to redirect cytotoxicity of several types of peripheral blood cells against relevant tumour targets. Among various effector cells, natural killer (NK) cells appear to play a role in defence against leukaemia. Here we report the successful chemical conjugation of monoclonal antibodies to CD33 and CD16 to create a bispecific antibody (BsAb 251 x 3G8). This bispecific antibody is capable of augmenting the killing of otherwise resistant leukaemia cells by peripheral blood lymphocytes (PBL), purified resting NK (R-NK) cells, and activated NK (A-NK) cells. BsAb 251 x 3G8 may play a role in the therapy of acute myeloid leukaemia (AML) through redirecting the cytotoxic activity of endogenous or adoptively transferred NK cells.
Silla
L M
LM
Division of Hematology/Bone Marrow Transplantation, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Chen
J
J
Zhong
R K
RK
Whiteside
T L
TL
Ball
E D
ED
D000208:Acute Disease; D018033:Antibodies, Bispecific / Q000502:physiology*; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000628:therapy; D017452:Receptors, IgG / Q000276:immunology*; D063268:Sialic Acid Binding Ig-like Lectin 3; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D017452:Receptors, IgG; D063268:Sialic Acid Binding Ig-like Lectin 3