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.
Purpose
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. Experimental design: 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.