A self-contained enzyme activating prodrug cytotherapy for preclinical melanoma

作者: Gwi-Moon Seo , Raja Shekar Rachakatla , Sivasai Balivada , Marla Pyle , Tej B. Shrestha

DOI: 10.1007/S11033-011-0720-7

关键词:

摘要: Gene-directed enzyme prodrug therapy (GDEPT) has been investigated as a means of cancer treatment without affecting normal tissues. This system is based on the delivery suicide gene, gene encoding an which able to convert its substrate from non-toxic cytotoxin. In this experiment, we have developed targeted therapeutic that completely contained within tumor-tropic cells and tested for melanoma in preclinical model. First, established double stable RAW264.7 monocyte/macrophage-like (Mo/Ma) containing Tet-On® Advanced intracellular carboxylesterase (InCE) expression. Second, loaded into cells, Mo/Ma. Third, activated prodrug, irinotecan, cytotoxin, SN-38. Our Mo/Ma homed lung melanomas after 1 day successfully delivered prodrug-activating enzyme/prodrug package tumors. We observed our significantly reduced tumor weights numbers activation InCE. Therefore, propose may be useful pulmonary metastatic tumors with minimal side effects, particularly if it combined other treatments.

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