IMPROVED ANTIBODY TARGETING WITH INTERFERON-ALPHA-2B CONJUGATE

This investigation is based on a hypothesis that a biological response modifier, interferon-alpha-2b (IFN), when conjugated with a specific monoclonal antibody (mAb) and given to tumor-bearing animals before th e administration of radiolabeled mBb, may not only augment the tumor u ptake but may also impede the liver and blood uptake, because the mAb associated with the conjugate may block nonspecific hepatic binding si tes and scavenge circulating antigens. ME 31.3 and anti-carcinoembryon ic antigen (CEA) F-6 (IgG-2a) specific for human melanoma and colorect al carcinoma, respectively, were chosen as prototype mAbs and conjugat ed with IFN-alpha-2b for evaluation in athymic nude mice bearing respe ctive experimental tumors. The mAb specificity for the tumor cell line was examined by binding assays and Kd values were determined to be 1. 96 x 10(-9) M and 5.9 x 10(-9) M for ME 31.3 and anti-CEA F-6, respect ively. Thirty micrograms of conjugate, prepared chemically and purifie d chromatographically (IFN-mAb:1:1), was administered intravenously to each animal and 3 h later followed by an intravenous injection of 20 mu g F(ab')(2) of corresponding mAb labeled with 300 mu Ci Tc-99m (1.5 Ci/mmol). Twenty-four hours later, in melanoma-bearing animals, not o nly did the tumor uptake increase, but also the liver uptake decreased by 75%. Tumor/muscle and tumor/blood ratios also enhanced by 200 and 500%, respectively. Consistent with ME 31.3, the tumor uptake with ant i-CEA F-6 also increased (p = 0.00) and the liver uptake decreased (p = 0.01). Similarly, tumor/muscle (p = 0.01) and tumor/blood (p = 0.02) ratios also increased significantly. Results indicate that IFN:mAb co njugate may improve diagnostic and therapeutic potential of mAbs, and is worthy of further studies.