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 -l monoclonal antibody (moAb) against primary and cultured Reed-Sternb erg cells present in Hodgkin's disease and anaplastic large-cell lymph omas (ALCLs). Examination of two ALCL cell Lines (Karpas 299 and Miche l) demonstrated cell surface expression of CD30. Incubation of these l ymphomas with two anti-CD30 moAbs that recognize the ligand-binding si te (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 w ere transferred i.v. into mice with severe combined immune deficiency, the mice developed extensive metastasis in the s.c., brain, or eye ti ssues. The treatment of mice with either M44 or HeFi-1 anti-CD30 moAbs resulted in significant increases in survival, with some mice remaini ng disease free for more than 100 days. Thus, anti-CD30 treatment is e fficacious for CD30(+) ALCL cell lines in vivo, and unconjugated anti- CD30 moAbs may be of potential clinical use.