Measurement of cetuximab and panitumumab-unbound serum EGFR extracellular domain using an assay based on slow off-rate modified aptamer (SOMAmer) reagents

Autor: Jonathan D. Vaught, Xiuqiang Wang, Charles M. Strom, Noh Jin Park, Christopher Bock, Weimin Sun, Angelica Diaz, Dana M. Goos-Root
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Receptor
ErbB-4
Receptor
ErbB-3
Receptor
ErbB-2
Cancer Treatment
Cetuximab
lcsh:Medicine
Pharmacology
Polymerase Chain Reaction
Epidermal growth factor
Basic Cancer Research
ERBB3
Epidermal growth factor receptor
lcsh:Science
Clinical Chemistry
Multidisciplinary
biology
Chemistry
Panitumumab
Antibodies
Monoclonal
Aptamers
Nucleotide
Clinical Laboratory Sciences
ErbB Receptors
Oncology
Medicine
medicine.drug
Research Article
Test Evaluation
medicine.drug_class
Aptamer
Antineoplastic Agents
Enzyme-Linked Immunosorbent Assay
Monoclonal antibody
Antibodies
Monoclonal
Humanized
Binding
Competitive
Antibody Therapy
ErbB
Diagnostic Medicine
medicine
Genetics
Cancer Genetics
Cancer Detection and Diagnosis
Early Detection
Humans
Biology
Clinical Genetics
Binding Sites
Clinical Laboratory Techniques
lcsh:R
Personalized Medicine
Reproducibility of Results
biology.protein
lcsh:Q
Biomarkers
Zdroj: PLoS ONE, Vol 8, Iss 8, p e71703 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: Background Response to cetuximab (Erbitux®) and panitumumab (Vectibix®) varies among individuals, and even those who show response ultimately gain drug resistance. One possible etiologic factor is differential interaction between the drug and target. We describe the development of an assay based on Slow Off-rate Modified Aptamer (SOMAmer™) reagents that can distinguish drug-bound from unbound epidermal growth factor receptor (EGFR). Methods This quantitative assay uses a SOMAmer reagent specific for EGFR extracellular domain (ECD) as a capturing reagent. Captured SOMAmer is quantitated using PCR. Linearity and accuracy (recovery) of the assay were assessed using normal sera and purified EGFR ECD. Results This EGFR ECD assay showed linearity between 2.5 and 600 ng/mL. Average recovery was 101%. The assay detected EGFR but showed little cross-reactivity to other ErbB proteins: 0.4% for ErbB2, 6.9% for ErbB3, and 1.3% for ErbB4. Preincubation of normal serum with either cetuximab or panitumumab resulted in a dose-dependent decrease in EGFR ECD levels measured using the SOMAmer assay; preincubation did not affect measurement with an ELISA. Conclusions This SOMAmer-based serum EGFR ECD assay accurately and specifically measures EGFR in serum. Detection of significant amounts of drug-unbound EGFR in patients undergoing cetuximab or panitumumab treatment could be an indicator of poor drug response. Further studies are needed to evaluate the utility of the assay as an indicator of drug efficacy or as a guide to dosing.
Databáze: OpenAIRE
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