Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts.
MCC-465 is an immunoliposome-encapsulated doxorubicin. The liposome is tagged with polyethylene glycol and the F(ab')2 of a monoclonal antibody named GAH, a human antibody obtained by the hybridoma technique. The epitope recognized by GAH is not well characterized, but human gastric, colorectal, and mammary cancer cells were GAH-positive, while the normal counterparts were GAH-negative. Pegylated liposome doxorubicin (PLD) and MCC-465 did not show significant antitumor activity against GAH-negative Caco-2 xenografts. On the other hand, MCC-465 exhibited significantly superior antitumor effects against GAH-positive WiDr-Tc and SW837 xenografts, compared with PLD. Immunohistochemistry with GAH revealed that 94% (100 of 106) of surgical specimens of colorectal cancer were GAH-positive. These results warrant a phase I clinical trial of MCC-465 for patients with metastatic colorectal cancer.
Hamaguchi
Tetsuya
T
Department of Medicine, Department of Pathology, President, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan.
Matsumura
Yasuhiro
Y
Nakanishi
Yukihiro
Y
Muro
Kei
K
Yamada
Yasuhide
Y
Shimada
Yasuhiro
Y
Shirao
Kuniaki
K
Niki
Hisae
H
Hosokawa
Saiko
S
Tagawa
Toshiaki
T
Kakizoe
Tadao
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000662:veterinary; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D006825:Hybridomas; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D008081:Liposomes; C474519:MCC465; D011092:Polyethylene Glycols; D004317:Doxorubicin