HLA class II antibodies recruit G-CSF activated neutrophils for treatment of B cell malignancies.
Monoclonal antibodies offer the potential to improve specificity of oncological therapy. However, future success in the clinic depends on enhancing antibody effector functions. Here, we suggest that target antigen selection may influence recruitment of effector cells for antibody therapy, and may improve the outcome of antibody treatment in patients. Comparing a wide range of antibodies to different B cell antigens, we found most were able to mediate antibody dependent cellular cytotoxicity (ADCC) with blood mononuclear cells (MNC). In direct contrast, however, polymorphonuclear granulocytes (PMN) from the same donors showed ADCC only with HLA class II antibodies. Based on this observation, we propose a therapeutic strategy with a combination of HLA class antibodies and G-CSF, the latter being required to increase number and activational state of neutrophils. In particular, we suggest using bispecific antibodies (BsAb) in which one arm binds to HLA class II on tumor cells, and the second to FcgammaRI on activated effector cells. The clinical potential of this approach for the treatment of B cell malignancies looks most attractive.
Valerius
T
T
Department of Medicine III, University Erlangen, Nürnberg, Germany. Thomas.Valerius@med3.med.uni-erlangen.de
Elsässer
D
D
Repp
R
R
Van de Winkel
J G
JG
Gramatzki
M
M
Glennie
M
M
D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D016179:Granulocyte Colony-Stimulating Factor