Pretargeted Radioimmunotherapy (RIT) with a Novel Anti-TAG-72 Fusion Protein

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/m²). All patients received 5 mCi of ¹¹¹In-DOTA-biotin for imaging and dosimetry purposes and patients 4–9 received 10 mCi/m2 of⁹⁰Y-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.