targeting cea in pancreas cancer xenografts with a mutated scfv-fc antibody fragment针对东航在异种移植胰腺癌症突变scfv-fc抗体片段.pdfVIP

Girgis et al. EJNMMI Research 2011, 1:24 /content/1/1/24 ORIGINAL RESEARCH Open Access Targeting CEA in Pancreas Cancer Xenografts with a Mutated scFv-Fc Antibody Fragment 1,3 2 2 2 2 1,3* Mark D Girgis , Tove Olafsen , Vania Kenanova , Katelyn E McCabe , Anna M Wu and James S Tomlinson Abstract Background: Sensitive antibody-based tumor targeting has the potential not only to image metastatic and micrometastatic disease, but also to be the basis of targeted therapy. The vast majority of pancreas cancers express carcinoembryonic antigen (CEA). Thus, we sought to evaluate the potential of CEA as a pancreatic cancer target utilizing a rapidly clearing engineered anti-CEA scFv-Fc antibody fragment with a mutation in the Fc region [anti- CEA scFv-Fc H310A]. Methods: Immunohistochemistry (IHC) with the antibody fragment was used to confirm expression of CEA on human pancreas cancer specimens. In vivo tumor targeting was evaluated by tail vein injection of I124-labeled anti- CEA scFv-Fc(H310A) into mice harboring CEA-positive and -negative xenografts. MicroPET/CT imaging was performed at successive time intervals. Radioactivity in blood and tumor was measured after the last time point. Additionally, unlabeled anti-CEA scFv-Fc(H310A) was injected into CEA-positive tumor bearing mice and ex vivo IHC was performed to identify the presence of the antibody to define the microscopic intratumoral pattern of targeting. Results: Moderate to strong staining by IHC was noted on 84% of our human pancreatic cancer specimens and was comparable to staining of our xenografts. Pancreas xenograft imaging with the radiolabeled anti-CEA scFv-Fc (H310A) antibody demonstrated average tumor/