【摘 要】
：
Ribosome-inactivating proteins such as ricin and Shiga-Like Toxin 1 (SLT-1) are highly effective at killing eukaryotic cells.Such molecules can be redirected to kill diseased cells by altering their r
【机 构】
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Department of Medical Biophysics Pharmaceutical Sciences The University of Toronto Canada
【出 处】
：
BIT Life Sciences 1st Annual World Cancer Congess-2008(2008中
论文部分内容阅读
Ribosome-inactivating proteins such as ricin and Shiga-Like Toxin 1 (SLT-1) are highly effective at killing eukaryotic cells.Such molecules can be redirected to kill diseased cells by altering their receptor specificity.We report the design of combinatorial SLT-1 libraries expressing a large repertoire of SLT-1 variants, each harboring a unique peptide ligand inserted within their cytotoxic A subunit.High-throughput cell-based cytotoxicity assays performed on thousands of purified SLT-1 variants led to the discovery of a single-chaln, ribosome-inactivating protein displaying selectivity for human melanoma cell-lines.Preclinical studies indicate that this protein variant increases the survival time of SCID mice bearing a human melanoma xenograft, while displaying no toxicity in mice (at 4mg/kg) and low immunogenicity The directed evolution of a ribosome-inactivating protein template represents a broad platform for identifying protein-based anticancer agents that are distinct from antibodies.
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