Effect of a chimeric anti-ganglioside GM2 antibody on ganglioside GM2-expressing human solid tumors in vivo.
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.
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
H
H
Fukumoto
K
K
Nishio
S
S
Ohta
N
N
Hanai
K
K
Fukuoka
Y
Y
Ohe
K
K
Sugihara
T
T
Kodama
N
N
Saijo
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D005678:G(M2) Ganglioside / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use
D000906:Antibodies; D011993:Recombinant Fusion Proteins; D005678:G(M2) Ganglioside; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003165:Complement System Proteins