Abstract
ABY-027 is a scaffold-protein-based cancer-targeting agent. ABY-027 includes the second-generation Affibody molecule Z(HER2:2891), which binds to human epidermal growth factor receptor type 2 (HER2). An engineered albumin-binding domain is fused to Z(HER2:2891) to reduce renal uptake and increase bioavailability. The agent can be site-specifically labeled with a beta-emitting radionuclide (177)Lu using a DOTA chelator. The goals of this study were to test the hypotheses that a targeted radionuclide therapy using [(177)Lu]Lu-ABY-027 could extend the survival of mice with HER2-expressing human xenografts and that co-treatment with [(177)Lu]Lu-ABY-027 and the HER2-targeting antibody trastuzumab could enhance this effect. Balb/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts were used as in vivo models. A pre-injection of trastuzumab did not reduce the uptake of [(177)Lu]Lu-ABY-027 in tumors. Mice were treated with [(177)Lu]Lu-ABY-027 or trastuzumab as monotherapies and a combination of these therapies. Mice treated with vehicle or unlabeled ABY-027 were used as controls. Targeted monotherapy using [(177)Lu]Lu-ABY-027 improved the survival of mice and was more efficient than trastuzumab monotherapy. A combination of therapies utilizing [(177)Lu]Lu-ABY-027 and trastuzumab improved the treatment outcome in comparison with monotherapies using these agents. In conclusion, [(177)Lu]Lu-ABY-027 alone or in combination with trastuzumab could be a new potential agent for the treatment of HER2-expressing tumors.