Ganglioside GM2 is expressed on the surface of
neuroblastoma and
glioblastoma cells, and may also be detected on
lung cancer cells. We reported previously that anti-
ganglioside GM2 antibody exhibited strong in vitro anti-
tumor activity against
adriamycin-resistant
cancer cells, which overexpressed
ganglioside GM2. In the present study, we examined the in vivo anti-
tumor effect of the chimeric anti-
ganglioside GM2 antibody, KM966, against human lung and
breast carcinoma cells, SBC-3 and MCF-7, and respective
adriamycin-resistant clones, SBC-3/ADM and AdrR MCF-7 in BALB/c nu/nu mice. Ratios of
tumor volume (T/C) between KM966-treated group and control group were 0.01 for SBC-3, 0.00 for SBC-3/ADM, 0.85 for MCF-7 and 0.34 for AdrR MCF-7 cells, respectively. Nude mice, which were pretreated with anti-
asialo GM1 antibody to remove natural killer cells, were transplanted with 4 x 10(7) of SBC-3 and SBC-3/ADM subcutaneously. Seven days later, when
tumors had grown to a diameter of over 8 mm, mice began to receive intravenous treatment of 120 microgram/mouse KM966 daily. Fourteen daily treatments induced regression to less than 4-mm diameter in 4/5 SBC-3
tumors and 5/5 of SBC-3/ADM
tumors. All SBC-3/ADM
tumors disappeared completely, suggesting that KM966 exerts a strong in vivo anti-
tumor effect on
ganglioside GM2-expressing
cancer cells. In KM966-treated mice, the surface of the
tumor cells stained positive with anti-human
IgG. In addition, numerous leukocytes had infiltrated into the
tumor mass. Antibody-dependent cell-mediated cytotoxicity (ADCC) of KM966 against
tumor cells was examined in vitro by (51)Cr-release assay and revealed that KM966 induces ADCC activity against
ganglioside GM2-expressing
tumors. Our results suggest that
immunotherapy using KM966 may be useful for the treatment of
ganglioside GM2-expressing solid
tumors.