A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo.
In order to target NK cells against the Hodgkin's-derived cell line L540, we developed bispecific monoclonal antibodies (Bi-MAbs) by somatic hybridization of the 2 mouse hybridoma cell line HRS-3 and A9 which produce monoclonal antibodies (MAbs) with reactivity against the Hodgkin and Reed-Sternberg cell-associated CD30 antigen and the CD16 antigen (Fc gamma III receptor), respectively. The CD16 MAb-producing cell line A9 was selected as a partner for HRS-3 because of its efficiency in inducing lysis of the A9 hybridoma cells by resting NK cells. The hybrid hybridoma cell line HRS-3/A9 produced the supernatant with the strongest bispecific reactivity and was repeatedly subcloned and used for ascites production. Crude supernatant and purified HRS-3/A9 Bi-MAb triggered specific lysis of the CD30+ Hodgkin's-derived cell line L540, but not of the CD30- cell line HPB-ALL by unstimulated peripheral-blood lymphocytes and NK-cell-enriched populations. Moreover, treatment of SCID mice bearing heterotransplanted human Hodgkin's tumors with HRS-3/A9 and human peripheral blood lymphocytes induced specific complete tumor regression in 10/10 animals. We thus report successful tumor treatment in an in vivo model using NK-cell-associated Bi-MAbs and show that the Bi-MAb HRS-3/A9 is an efficient promoter of the anti-tumor effects of NK cells in vitro and in vivo.
Hombach
A
A
Medizinische Klinik, Universität des Saarlandes, Homburg/Saar, Germany.
Jung
W
W
Pohl
C
C
Renner
C
C
Sahin
U
U
Schmits
R
R
Wolf
J
J
Kapp
U
U
Diehl
V
V
Pfreundschuh
M
M
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006689:Hodgkin Disease / Q000276:immunology* / Q000628:therapy; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007525:Isoelectric Focusing; D017730:Ki-1 Antigen / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D017452:Receptors, IgG / Q000276:immunology*; D016539:Reed-Sternberg Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D017730:Ki-1 Antigen; D017452:Receptors, IgG