Pretargeted radioimmunotherapy (RIT) with a novel anti-TAG-72 fusion protein

Academic Article

Abstract

  • Pretargeted radioimmunotherapy (RIT) increases the dose of radionuclide delivered to tumor sites while limiting radiation to normal tissues. The three components in Pretarget® include a streptavidin-containing targeting molecule, a synthetic clearing agent (sCA), and 90Y and/or 111In-DOTA-biotin. This trial determined the feasibility and safety of using a genetically engineered fusion protein directed to TAG-72 as the targeting agent. Nine (9) patients with metastatic colorectal cancer (TAG-72+) received 160 mg/m2 of CC49Fusion protein intravenously (i.V.), followed by the sCA, 45 mg/m2 i.v. Twenty-four (24) hours later, patients received radiolabeled DOTA-biotin (either 0.65 or 1.3 mg/m 2). All patients received 5 mCi of 111In-DOTA-biotin for imaging and dosimetry purposes and patients 4-9 received 10 mCi/m2 of 90Y-DOTA-biotin as well. The mean plasma T1/2 of CC49Fusion protein was 23 ± 6 hours. Greater than 95% of the circulating CC49Fusion protein was eliminated from the circulation within 6 hours of sCA administration. The radiolabeled DOTA-biotin rapidly localized to tumor sites while the unbound fraction was rapidly excreted. The mean tumor-to-marrow radiation dose ratio was 139:1 and mean tumor:whole body was 56:1. No infusion-related, renal, hepatic, or hematologic toxicities were noted. CC49Fusion protein performs well in a pretargeted RIT schema, and further study with escalating doses of 90Y should be pursued. This strategy has the potential to deliver effective radiation tumor doses to TAG-72+ tumors. © Mary Ann Liebert, Inc.
  • Digital Object Identifier (doi)

    Author List

  • Forero-Torres A; Shen S; Breitz H; Sims RB; Axworthy DB; Khazaeli MB; Chen KH; Percent I; Besh S; LoBuglio AF
  • Start Page

  • 379
  • End Page

  • 390
  • Volume

  • 20
  • Issue

  • 4