Fractionated radioimmunotherapy with ⁹⁰Y-labeled fully human anti-CEA antibody

Carcinoembryonic antigen (CEA) is an attractive target molecule of radioimmunotherapy (RIT). To enhance RIT's therapeutic efficacy, the fractionation of radiolabeled antibody doses is an attractive strategy. In this study, a fully human anti-CEA monoclonal antibody (mAb) C2-45 was selected by virtue of its lack of immunogenicity, and the effectiveness of fractionated RIT with yttrium-90 (⁹⁰Y)-labeled mAb C2-45 was evaluated. In LS180 tumor-bearing mice, indium-111 (¹¹¹In)-labeled mAb C2-45 showed high and persistent tumor accumulation. Therapeutic studies were performed with single doses of ⁹⁰Y-mAb C2-45 (100 or 200 μCi) or double doses of 100 μCi ⁹⁰Y-mAb C2-45 at different intervals (5, 10, and 15 days). All ⁹⁰Y-mAb C2-45-treated mice showed inhibition of tumor progression, while the time to tumor progression was much longer in both the 200-μCi-treated group and the double 100-μCi-treated group than in the single 100-μCi-treated group. The therapeutic effect of the double 100 μCi administration at days 0 and 15 lasted significantly longer than that in the other treatment groups. These findings indicate that ⁹⁰Y-mAb C2-45 may be a promising agent for the treatment of CEA-positive cancer and that the fractionation of ⁹⁰Y-labeled antibody doses could enhance the therapeutic effect if performed according to an appropriate protocol.