The development of BRAF-I resistance in BRAFV600E melanoma underlies the need to develop strategies to counteract this resistance. It has been shown that administration of heat shock protein 90 (HSP90) inhibitors can counteract multiple mechanisms which drive BRAF-I resistance by reactivation of MAPK and activation of PI3K/AKT pathway. However the clinical application of this strategy is hampered the high toxicity associated with administration of currently available HSP90 inhibitors. To overcome this limitation we have developed a novel monoclonal antibody (mAb), named W9, which recognizes an extracellular epitope of glucose regulated protein of 94 kDa (Grp94), a member of the HSP90 family. The mAb W9 defined Grp94-epitope is selectively expressed on malignant cells but is not detectable on normal cells. Therefore targeting Grp94-epitope by mAb W9 is expected to cause limited if any side effects. The mAb W9 was found to increase and restore the sensitivity to BRAF-I of BRAFV600E melanoma cells including cells which have acquired BRAF-I resistance because of PDGFRα upregulation.
Author information
Authors and Affiliations
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Sabbatino, F., Favoino, E., Wang, Y. et al. Grp94-specific monoclonal antibody to counteract BRAF inhibitor resistance in BRAFV600E melanoma. J Transl Med 13 (Suppl 1), K12 (2015). https://doi.org/10.1186/1479-5876-13-S1-K12
Published:
DOI: https://doi.org/10.1186/1479-5876-13-S1-K12