In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product.
The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2-overexpressing SK-BR-3 cell line. In vivo treatment of severe combined immunodeficient (SCID) mice carrying the c-erbB-2-overexpressing 4-1ST human gastric carcinoma xenograft with 4hu4D5 revealed that the recombinant protein had potent anti-tumour activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might perform better in patients than predicted from preclinical studies.
Tokuda
Y
Y
Department of Surgery, Tokai University School of Medicine, Kanagawa, Japan.
Ohnishi
Y
Y
Shimamura
K
K
Iwasawa
M
M
Yoshimura
M
M
Ueyama
Y
Y
Tamaoki
N
N
Tajima
T
T
Mitomi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins