Abstract 1778: Nimotuzumab, a humanized antiepidermal growth factor receptor antibody, interacts with EGFRvIII

Download
  1. Get@NRC: Abstract 1778: Nimotuzumab, a humanized antiepidermal growth factor receptor antibody, interacts with EGFRvIII (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1158/1538-7445.AM10-1778
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleCancer Research
ISSN0008-5472
1538-7445
Volume70
Issue8 Supplement
Pages17781778
AbstractIntroduction: Glioblastomas frequently overexpress a variant form of EGFR, called variant III (EGFRvIII), which has an in-frame deletion of an 801-bp sequence in the extracellular domain. EGFRvIII does not bind EGF ligand but exhibits constitutive kinase activity that results in enhanced transformation, reduced apoptosis, and resistance to therapy. Nimotuzumab (Nmab) is an EGFR-targeting antibody that has demonstrated encouraging results in early clinical trials treating adult and pediatric brain tumors. Here we present data characterizing the interaction of Nmab with EGFRvIII. Methods: Binding of Nmab to the extracellular domain of wtEGFR and EGFRvIII was first characterized by SPR biosensor analysis: Nmab was captured via its Fc domain and varying concentrations of EGFRvIII and EGFRwt were flowed. Flow cytometry analysis was subsequently performed using a parental U87MG glioblastoma cell line and derivatives which were engineered to overexpress either wtEGFR or EGFRvIII. Results: Nmab bound EGFRvIII and EGFRwt with similar affinity, which was in the 10−8 M range. This KD is consistent with the previously reported affinity constant of Nmab for EGFRwt (Telavera et al, 2009). Binding was further analyzed by flow cytometry. Nmab bound both EGFRwt and EGFRvIII expressed on the surface of parental U87MG, U87MG EGFRvIII and U87MG wtEGFR cells. Additional data concerning effects of Nmab on EGFRvIII expressing cell lines will be presented. Conclusion: Nmab binds to wtEGFR and EGFRvIII with similar affinity, which supports development of the antibody as a therapeutic for glioblastoma. In U87MG glioblastoma cells, synergistic activity of Nmab in combination with radiotherapy has been previously reported (Diaz Miqueli et al, 2009). Nmab is currently being tested in an advanced randomized study in the first line setting for the treatment of adult glioma. Nmab is being tested in combination with radiation plus temozolomide, vs radiation plus temozolomide alone, with preliminary results expected in the second half of 2010.
Publication date
PublisherAmerican Association for Cancer Research
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number23001786
Export citationExport as RIS
Report a correctionReport a correction
Record identifier43443b1e-1317-4128-add5-1985a326a41b
Record created2017-04-06
Record modified2017-04-06
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)