Cetuximab-Based Immunotherapy and Radioimmunotherapy of Head and Neck Squamous Cell Carcinoma
Open Access
- 31 March 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 16 (7), 2095-2105
- https://doi.org/10.1158/1078-0432.ccr-09-2495
Abstract
Purpose: To show the relationship between antibody delivery and therapeutic efficacy in head and neck cancers, in this study we evaluated the pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR)–targeted immunotherapy and radioimmunotherapy by quantitative positron emission tomography (PET) imaging. Experimental Design: EGFR expression on UM-SCC-22B and SCC1 human head and neck squamous cell cancer (HNSCC) cells were determined by flow cytometry and immunostaining. Tumor delivery and distribution of cetuximab in tumor-bearing nude mice were evaluated with small animal PET using 64Cu-DOTA-cetuximab. The in vitro toxicity of cetuximab to HNSCC cells was evaluated by MTT assay. The tumor-bearing mice were then treated with four doses of cetuximab at 10 mg/kg per dose, and tumor growth was evaluated by caliper measurement. FDG PET was done after the third dose of antibody administration to evaluate tumor response. Apoptosis and tumor cell proliferation after cetuximab treatment were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki-67 staining. Radioimmunotherapy was done with 90Y-DOTA-cetuximab. Results: EGFR expression on UM-SCC-22B cells is lower than that on SCC1 cells. However, the UM-SCC-22B tumors showed much higher 64Cu-DOTA-cetuximab accumulation than the SCC1 tumors. Cetuximab-induced apoptosis in SCC1 tumors and tumor growth was significantly inhibited, whereas an agonistic effect of cetuximab on UM-SCC-22B tumor growth was observed. After cetuximab treatment, the SCC1 tumors showed decreased FDG uptake, and the UM-SCC-22B tumors had increased FDG uptake. UM-SCC-22B tumors are more responsive to 90Y-DOTA-cetuximab treatment than SCC1 tumors, partially due to the high tumor accumulation of the injected antibody. Conclusion: Cetuximab has an agonistic effect on the growth of UM-SCC-22B tumors, indicating that tumor response to cetuximab treatment is not necessarily related to EGFR expression and antibody delivery efficiency, as determined by PET imaging. Although PET imaging with antibodies as tracers has limited function in patient screening, it can provide guidance for targeted therapy using antibodies as delivery vehicles. Clin Cancer Res; 16(7); 2095–105. ©2010 AACR.Keywords
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This publication has 44 references indexed in Scilit:
- The Effect of Combination Anti–Endothelial Growth Factor Receptor and Anti–Vascular Endothelial Growth Factor Receptor 2 Targeted Therapy on Lymph Node MetastasisJAMA Otolaryngology–Head & Neck Surgery, 2009
- Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma MultiformeClinical Cancer Research, 2008
- Platinum-Based Chemotherapy plus Cetuximab in Head and Neck CancerThe New England Journal of Medicine, 2008
- Combined Inhibition of c-Src and Epidermal Growth Factor Receptor Abrogates Growth and Invasion of Head and Neck Squamous Cell CarcinomaClinical Cancer Research, 2008
- Cancer Statistics, 2008CA: A Cancer Journal for Clinicians, 2008
- KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With CetuximabJournal of Clinical Oncology, 2008
- PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patientsBritish Journal of Cancer, 2007
- Epidermal growth factor receptor (EGFR) signaling in cancerGene, 2006
- Cetuximab and Irinotecan Interact Synergistically to Inhibit the Growth of Orthotopic Anaplastic Thyroid Carcinoma Xenografts in Nude MiceClinical Cancer Research, 2006
- Phase II Trial of Cetuximab in Patients With Refractory Colorectal Cancer That Expresses the Epidermal Growth Factor ReceptorJournal of Clinical Oncology, 2004