In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy.
OBJECTIVE
We examined the possible efficacy of the yttrium-90 ((90)Y)-labeled anti-CDH3/P-cadherin mouse monoclonal antibody (MAb-6) in radioimmunotherapy (RIT) for lung and colorectal cancers that express CDH3/P-cadherin.


METHODS
MAb-6 was established using genetic immunization. The biodistribution of MAb-6 in nude mice with lung and colorectal cancers was examined by administering indium-111((111)In)-labeled MAb-6 to mice. The mice were prepared by inoculation of CDH3/P-cadherin-positive (EBC1, H1373, and SW948) and CDH3/P-cadherin-negative (A549 and RKO) tumor cells. Therapeutic effects and toxicity were investigated by administration of (90)Y-labeled MAb-6 ((90)Y-MAb-6) to EBC, H1373, and SW948-inoculated mice.


RESULTS
Our in vivo results confirmed the specific binding of MAb-6 to tumor cells after intravenous injections of (111)In-labeled MAb-6 to mice with tumors expressing CDH3/P-cadherin. A single intravenous injection of (90)Y-MAb-6 (100 μCi) significantly suppressed tumor growth in mice with tumors expressing CDH3/P-cadherin. Furthermore, two injections of (90)Y-MAb-6 led to complete tumor regression in H1373-inoculated mice without any detectable toxicity.


CONCLUSIONS
Our findings demonstrate that CDH3/P-cadherin-targeting RIT with (90)Y-MAb-6 is a promising strategy for the treatment for cancers expressing CDH3/P-cadherin.
Department of Diagnosis of Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan. h-yoshioka@oncotherapy.co.jp
Hiroki
H
Yoshioka
Shinji
S
Yamamoto
Hirofumi
H
Hanaoka
Yasuhiko
Y
Iida
Pramila
P
Paudyal
Tetsuya
T
Higuchi
Hideyuki
H
Tominaga
Noboru
N
Oriuchi
Hidewaki
H
Nakagawa
Yasuhiro
Y
Shiba
Koji
K
Yoshida
Ryuji
R
Osawa
Toyomasa
T
Katagiri
Takuya
T
Tsunoda
Yusuke
Y
Nakamura
Keigo
K
Endo
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D015820:Cadherins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000532:radiotherapy*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016499:Radioimmunotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015820:Cadherins; D015021:Yttrium Radioisotopes