ENHANCED ANTITUMOR EFFECTS OF CD20 OVER CD19 MONOCLONAL-ANTIBODIES INA NUDE-MOUSE XENOGRAFT MODEL

We used a nude mouse xenograft tumor model to compare the efficacy of unconjugated CD19 and CD20 mAbs (IgG2a subclass) in mediating antilymp homa effects. Treatment with the CD20 mAbs NKI-B20 and BCA-B20 resulte d in a drastic decrease in tumor take rate (P < 0.0001) in comparison to controls, whereas the CD19 mAb CLB-CD19 was ineffective. Tumor grow th rates were reduced by both CD19 and CD20 (P < 0.0001). The decrease in growth rate induced by NKI-B20 or BCA-B20 was larger than that ind uced by CLB-CD19 (P = 0.0022). In vitro experiments showed that NKI-B2 0 or BCA-B20 are more powerful than CLB-CD19 in mediating lysis by int erleukin 2-activated natural kilter cells. No difference was observed between different isotypes (IgG1, IgG2a, IgG2b) of the switch variants of NKI-B20 or CLB-CD19. A positive correlation between antigen densit y and the sensitivity to antibody-dependent cellular cytotoxicity was demonstrated with human lymphoblastoid B cells, JY, transfected with c DNA encoding the human CD19 antigen that expressed high levels of this antigen. These cells are more efficiently killed by natural killer ce lls when coated with CLB-CD19 mAbs than JY wild-type cells that expres s 1 log lower levels of the CD19 antigen. Antibody-dependent cellular cytotoxicity experiments with thioglycolate-activated macrophages show a more complex relationship between antigen density, isotype of the m Ab, and cytotoxicity. BCA-B20 (IgG2a) and CLB-CD19 (IgG2a) and all iso types of NKI-B20 mediated strong cytotoxicity, whereas CLB-CD19 isotyp es IgG1 and IgG2b were associated with limited cytotoxicity. Prolifera tion of Daudi cells was inhibited with high concentrations of all isot ypes of CLB-CD19, but not with any of the CD20 mAbs. To our knowledge this is the first report showing that the antitumor effects in vivo of unconjugated CD20 mAbs are far superior to those of CD19 mAbs.