%0 Journal Article
%T An evolved ribosome-inactivating protein targets and kills human melanoma cells in vitro and in vivo
%A Melissa C Cheung
%A Leigh Revers
%A Subodini Perampalam
%A Xin Wei
%A Reza Kiarash
%A David E Green
%A Aws Abdul-Wahid
%A Jean Gari¨¦py
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-28
%X SLT-1AIYSNKLM was able to kill 7 of 8 human melanoma cell lines. This scRIP binds to 518-A2 human melanoma cells with a dissociation constant of 18 nM, resulting in the blockage of protein synthesis and apoptosis in such cells. Biodistribution and imaging studies of radiolabeled SLT-1AIYSNKLM administered intravenously into SCID mice bearing a human melanoma xenograft indicate that SLT-1AIYSNKLM readily accumulates at the tumor site as opposed to non-target tissues. Furthermore, the co-administration of SLT-1AIYSNKLM with DTIC resulted in tumor regression and greatly increased survival in this mouse xenograft model in comparison to DTIC or SLT-1AIYSNKLM treatment alone (115 day median survival versus 46 and 47 days respectively; P values < 0.001). SLT-1AIYSNKLM is stable in serum and its intravenous administration resulted in modest immune responses following repeated injections in CD1 mice.These results demonstrate that the evolution of a scRIP template can lead to the discovery of novel cancer cell-targeted compounds and in the case of SLT-1AIYSNKLM can specifically kill human melanoma cells in vitro and in vivo.The incidence of melanoma has been rising in the United States for the past sixty years [1,2]. Despite prevention efforts, it remains the second leading cause of lost productive years among all cancers, and is responsible for more than 7,000 deaths annually [2]. Novel melanoma-targeted therapeutic agents are needed to improve prognosis, since traditional treatments such as dacarbazine (DTIC) and IL-2 only yield a 5% survival advantage of more than five years for patients with advanced melanoma [2]. Currently, targeted agents such as monoclonal antibodies and recombinant proteins account for more than a quarter of all cancer therapeutics that have been newly approved or are presently in clinical trials [3,4]. Although effective in delaying the progression of certain cancers, naked antibodies such as Herceptin and Avastin do not cure the disease [5-7]. This
%U http://www.molecular-cancer.com/content/9/1/28