The effect of intravenous and intra-tumoural chemotherapy using a monoclonal antibody-drug conjugate in a xenograft model of pancreatic cancer.
In order to investigate the efficacy of the intra-tumoural administration of an anticancer drug-monoclonal antibody conjugate in athymic nude mice bearing xenografts of a human pancreatic carcinoma, we examined the clearance of the murine monoclonal antibody A7 from the xenografts after intravenous or intra-tumoural administration and measured the antitumour effect of neocarzinostatin conjugated to MAb A7 following intravenous or intra-tumoural injection. Compared with 125I-labelled normal mouse IgG, a larger amount of 125I-labelled A7 remained in the tumour after both intravenous and intra-tumoural injection, and a significantly larger amount of 125I-labelled A7 remained in the tumour after intra-tumoural injection than that after intravenous injection. Moreover, a larger amount of 125I-labelled A7-NCS localized in the tumour after intra-tumoural injection than that after intravenous injection. Neocarzinostatin conjugated to MAb A7 showed greater activity against human pancreatic cancer than neocarzinostatin alone after both intravenous and intra-tumoural administration. Tumour growth was suppressed completely by the intra-tumoural administration of A7-NCS at a dose that did not suppress tumour growth via the intravenous route. These observations suggest that the intra-tumoural injection of neocarzinostatin conjugated to MAb A7 offers promise in treating pancreatic carcinoma.
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
E
E
Otsuji
T
T
Yamaguchi
H
H
Tsuruta
Y
Y
Yata
H
H
Nishi
K
K
Okamoto
K
K
Taniguchi
M
M
Kato
T
T
Kotani
K
K
Kitamura
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D015552:Injections, Intralesional; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000008:administration & dosage / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D009353:Zinostatin