In vivo antitumor effects of unconjugated CD30 monoclonal antibodies on human anaplastic large-cell lymphoma xenografts.
CD30 is a M(r) 120,000 surface antigen identified originally by the Ki-1 monoclonal antibody (moAb) against primary and cultured Reed-Sternberg cells present in Hodgkin's disease and anaplastic large-cell lymphomas (ALCLs). Examination of two ALCL cell lines (Karpas 299 and Michel) demonstrated cell surface expression of CD30. Incubation of these lymphomas with two anti-CD30 moAbs that recognize the ligand-binding site (M44 or HeFi-1) resulted in significant growth inhibition in vitro, with significant decreases in cell viability. Another anti-CD30 moAb, Ber-H2, which recognizes a determinant not involved in ligand binding, had no effect on ALCL growth in vitro. When these human ALCL lines were transferred i.v. into mice with severe combined immune deficiency, the mice developed extensive metastasis in the s.c., brain, or eye tissues. The treatment of mice with either M44 or HeFi-1 anti-CD30 moAbs resulted in significant increases in survival, with some mice remaining disease free for more than 100 days. Thus, anti-CD30 treatment is efficacious for CD30+ ALCL cell lines in vivo, and unconjugated anti-CD30 moAbs may be of potential clinical use.
Tian
Z G
ZG
Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
Longo
D L
DL
Funakoshi
S
S
Asai
O
O
Ferris
D K
DK
Widmer
M
M
Murphy
W J
WJ
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002455:Cell Division; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis / Q000276:immunology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000628:therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen