Characterization and biodistribution of a mouse/human chimeric antibody directed against pancreatic cancer mucin.
BACKGROUND
Nd2 is a murine monoclonal antibody (MoAb) directed against purified mucins of the human pancreatic cancer cell line SW1990. The authors previously reported promising results with Nd2 for immunotargeting pancreatic cancer. However, murine MoAbs induce human anti-mouse antibodies (HAMAs), a serious problem for clinical use. Mouse/human chimeric antibodies may be less immunogenic and therefore reduce the incidence of HAMAs. In this study, the binding affinity, tumor specificity, biodistribution, and immunoimaging of chimeric Nd2 were evaluated.


METHODS
The affinity of chimeric Nd2 was evaluated by competition radioimmunoassay and Scatchard analysis using 125I-chimeric Nd2, 125I-murine Nd2, and SW1990 mucin. Immunoreactivity against pancreatic cancer tissues was examined histochemically by the avidin-biotin peroxidase complex method. The biodistribution of the MoAbs was examined in athymic nude mice bearing SW1990 xenografts that were administered intravenous 125I-labeled chimeric or murine Nd2. 111In-chimeric Nd2 was injected into the same xenograft models, and scintigrams were obtained on day 3.


RESULTS
Affinity analysis and immunohistochemical studies showed that chimeric Nd2 had the same affinity to SW1990 mucin and the same specificity for pancreas cancer tissues as murine Nd2. Intravenous administration of 125I-chimeric Nd2 resulted in a maximum tumor accumulation of 43% of the initial dose/gram of tumor, which was almost identical to the accumulation of 125I-murine Nd2. Distinct immunoscintigrams of tumors in nude mice were obtained with 111In-chimeric Nd2.


CONCLUSIONS
Chimeric Nd2 may have clinical potential in the radioimmunodetection and immunotherapy of pancreatic cancer.
Hirayama
K
K
First Department of Surgery, Osaka City University Medical School, Japan.
Chung
Y S
YS
Sawada
T
T
Kim
Y S
YS
Sowa
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000915:Antibody Affinity; D000951:Antigens, Neoplasm / Q000276:immunology; D002678:Chimera; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology*; D016719:Radioimmunodetection; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D009077:Mucins; D011994:Recombinant Proteins