Comparison of growth inhibition of a human ovarian adenocarcinoma cell line by free monoclonal antibodies and their corresponding antibody-recombinant ricin A chain immunotoxins.
Four mouse monoclonal antibodies (mAb) (8C, IgG2a; M2A, IgG2a; M2D, IgG2b; 10B, IgG1) directed against the human ovarian adenocarcinoma cell line HEY were compared for their ability in the free form and as immunotoxins made with recombinant ricin A chain (rRA) to inhibit the growth of HEY cells. For in vitro studies cultured HEY cells were assayed for protein synthesis and plated in agarose to form colonies, and for in vivo studies they were injected intraperitoneally (i.p.) into BALB/c nu/nu (nude) mice at a challenge dose (3 X 10(5) cells) which produced carcinomatosis with ascites, leading to death 30 days following injection. In the free form, mAB 8C was the most potent in inhibiting colony formation in the complement (C)-mediated and ADCC (antibody-dependent cell-mediated cytoxicity) assays in vitro. This mAb was also the only one capable of prolonging survival of mice, both in tumor cell neutralization, and tumor growth inhibition experiments. The four mAb-rRA immunotoxins were effective in inhibiting protein synthesis in vitro in the presence of 10(-7) M monensin. However, in vivo, only 8C-rRA and M2A-rRA were capable of prolonging survival of mice in tumor growth inhibition experiments. Our results suggest that mAb 8C might be useful in the free form and as an 8C-rRA immunotoxin for i.p. immunotherapy of ovarian cancer.
Ettenson
D
D
Department of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada.
Sheldon
K
K
Marks
A
A
Houston
L L
LL
Baumal
R
R
D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002455:Cell Division; D002460:Cell Line; D005260:Female; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000628:therapy; D011994:Recombinant Proteins / Q000627:therapeutic use; D012276:Ricin / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011994:Recombinant Proteins; D012276:Ricin