apeutics linical Development ermal Growth Factor Receptor – Targeted ioimmunotherapy of Human Head and Neck Cancer ografts Using 90 Y - Labeled Fully Human Ther ibody Panitumumab

wnloade itumumab (ABX-EGF or Vectibix), the first fully human monoclonal antibody targeting epidermal h factor receptor (EGFR), was approved by the Food and Drug Administration for treatment of ts with metastatic colorectal cancer. Here, we report for the first time the radioimmunotherapy of EGFR-positive human head and neck cancer in a nude mouse model using pure β emitter eled panitumumab. Biodistribution and planar γ-imaging studies were carried out with In-panitumumab. The RIT efficacy of Y-DOTA-panitumumab was evaluated in UM-SCC-22B tumor . CD31, Ki67, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling, and H&E g were done on UM-SCC-22B tumor sections after treatment. The tumor uptake of In-DOTAmumab in UM-SCC-22B tumor-bearing nude mice was 26.10 ± 4.93, 59.11 ± 7.22, 44.57 ± 9.80, ± 7.76, and 14.86 ± 7.23 % injected dose per gram of tissue at 4, 24, 72, 120, and 168 hours after on, respectively. Immunotherapy with cold panitumumab (four doses of 10 mg/kg) did not cause cant antitumor effect. RIT with a single dose of 100 μCi Y-DOTA-panitumumab caused significant growth delay and improved the survival in UM-SCC-22B tumor model. A single dose of 200 μCi TA-panitumumab led to almost complete tumor regression (tumor volumes were 34.83 ± 11.11 and 56.02 ± 39.95 mm on days 0 and 46 after treatment, respectively). Histopathologic analysis ors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of TA-panitumumab. The high tumor uptake and prolonged tumor retention, as well as effective Y-DO therapy, reveal that Y-DOTA-panitumumab may be a promising radioimmunotherapeutic agent to treat EGFR-positive solid tumors. Mol Cancer Ther; 9(8); 2297–308. ©2010 AACR.