Enhanced clearance of radiolabeled murine monoclonal antibody by a syngeneic anti‐idiotype antibody in tumor‐bearing nude mice

A syngeneic anti‐idiotype monoclonal antibody (MAb) (CM‐II) directed against an anti‐carcinoembryonic antigen (CEA) murine MAb (NP‐4) was evaluated as a second antibody (SA) to promote the rapid clearance of radiolabeled NP‐4 from the blood. Initial studies confirmed that CM‐II IgG removed 131 ‐NP‐4 IgG from the blood as effectively as a polyclonal donkey anti‐goat IgG removed 131 I‐goat IgG. However, use of an F(ab′)2 in place of either the NP‐4 or CM‐II IgG was not as effective in removing primary radiolabeled antibody, despite the formation of high‐molecular‐weight complexes. In accordance with previous results, the timing and dose of the SA injection was critical for optimizing tumor uptake and improving tumor/non‐tumor ratios. In nude mice bearing GW‐39 human colonic tumor xenografts, a delay in the injection of CM‐II by 48 hr after injection of radiolabeled NP‐4 was optimal, since this allowed maximum tumor accretion. At a 200:1 CM‐II:NP‐4 ratio, tumor uptake was reduced, suggesting inhibition of NP‐4 binding to CEA within the tumor. Despite optimizing tumor uptake by delaying SA injection and adjusting its dose, the percentage of 131 ‐NP‐4 in the tumor decreased 2‐ to 3‐fold within 2 days after CM‐II injection. A similar effect was seen for 111 In‐labeled NP‐4 IgG with CM‐II. Injection of excess unlabeled NP‐4 given to block CM‐II shortly after its injection failed to curtail the loss of NP‐4 from the tumor. Our results suggest that high blood levels of MAb are important for sustaining NP‐4 in the tumor. Radiation‐dose predictions derived from biodistribution studies indicate that a higher tumor dose may be delivered using the SA method than with either 131 I‐NP‐4 IgG or F(ab′) 2 alone. Use of the SA method with 90 Y‐labeled NP‐4 IgG, as modeled from biodistribution studies with 11 In‐NP‐4 IgG, would likely be limited by liver toxicity.