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

• Published in: Cancer biotherapy & radiopharmaceuticals Vol. 20; no. 4; pp. 379 - 390
• Main Authors: Forero-Torres, Andres, Shen, Sui, Breitz, Hazel, Sims, Robert B, Axworthy, Don B, Khazaeli, M B, Chen, Kuang-Ho, Percent, Ivor, Besh, Stephen, LoBuglio, Albert F, Meredith, Ruby F
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.08.2005
• Subjects: Adenocarcinoma - therapy; Aged; Antigens, Neoplasm - therapeutic use; Biotin - analogs & derivatives; Biotin - chemistry; Biotin - pharmacology; Clinical Trials as Topic; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Gamma Cameras; Gastrointestinal Neoplasms - therapy; Glycoproteins - therapeutic use; Humans; Indium Radioisotopes; Liver Neoplasms - secondary; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds - pharmacology; Radioimmunotherapy - methods; Radioisotopes; Radiometry; Radiopharmaceuticals - therapeutic use; Recombinant Fusion Proteins - chemistry; Rhenium; Streptavidin - pharmacology; Time Factors; Treatment Outcome; Yttrium Radioisotopes - therapeutic use
• ISSN: 1084-9785; 1557-8852
• DOI: 10.1089/cbr.2005.20.379

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 (90)Y and/or (111)In-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/m(2) of CC49Fusion protein intravenously (i.v.), followed by the sCA, 45 mg/m(2) 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 (111)In-DOTA-biotin for imaging and dosimetry purposes and patients 4-9 received 10 mCi/m2 of (90)Y-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 (90)Y should be pursued. This strategy has the potential to deliver effective radiation tumor doses to TAG- 72+ tumors.