Intratumoral injection of an adriamycin immunoconjugate against human pancreatic cancer xenografts.
We have evaluated the effect of an adriamycin conjugate of monoclonal antibody Nd2 (ADM-Nd2) on the growth rate of SW1990 xenografts grown subcutaneously in athymic nude mice. Intravenous or intraperitoneal administration of radiolabeled Nd2 resulted in a maximum tumor accumulation of approximately 45% of the initial dose/g of tumor 3-7 days after administration. However, administration into the tumor produced retention of 1200%ID/g 1 day after, with 50% of this high value remaining even at 7 days after administration. In contrast, intratumoral administration of a non-specific immunoglobulin showed a lower initial retention and rapid loss of label. Both intravenously and intratumorally administered ADM-Nd2 reduced the growth rate of SW1990 xenografts. While a single intravenous administration arrested growth for about two weeks, a single intratumoral injection prevented any increase in tumor size even 45 days after administration. Xenografts treated with ADM-Nd2 showed degenerative changes at the histological level. Neither Nd2 alone nor Adriamycin alone inhibited growth when administered at the same dose as the conjugate.
Kondo
Y
Y
First Department of Surgery, Osaka City University Medical School.
Chung
Y S
YS
Sawada
T
T
Inui
A
A
Yamashita
Y
Y
Hirayama
K
K
Nakata
B
B
Ho
J J
JJ
Kim
Y S
YS
Sowa
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000276:immunology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000627:therapeutic use; D015552:Injections, Intralesional; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009077:Mucins / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D018796:Immunoconjugates; D009077:Mucins; D009363:Neoplasm Proteins; D004317:Doxorubicin