Salmonella-based tumor-targeted cancer therapy: Tumor amplified protein expression therapy (TAPET™) for diagnostic imaging Journal Article
| Authors: | Tjuvajev, J.; Blasberg, R.; Luo, X.; Zheng, L. M.; King, I.; Bermudes, D. |
| Article Title: | Salmonella-based tumor-targeted cancer therapy: Tumor amplified protein expression therapy (TAPET™) for diagnostic imaging |
| Abstract: | In preclinical studies, genetically engineered Salmonella have the ability to localize, selectively accumulate, and persist within transplantable murine tumors, spontaneous murine tumors and human tumor xenographs, and can express therapeutic proteins at high levels. These strains of engineered non-virulent Salmonella typhimurium display the capacity to accumulate and grow selectively in a variety of tumor types and to inhibit the growth of primary and metastatic tumors following intravenous injection into tumor-bearing mice. One strain of the bacteria (VNP20009) which has endogenous antitumor activity is currently in Phase I clinical trials. The bacteria are highly attenuated and genetically stable. The combination of the lipid mutation and the purine auxotrophy attenuate the virulence of the bacteria by greater than 10 000-fold and enhance the specificity of the bacteria for tumor tissue. These bacteria have been found to be safe in mice, pigs and monkeys when administered intravenously. Second-generation Salmonella vectors will be developed to include transgenes that will express therapeutic agents and reporter transgenes for non-invasive imaging. We have performed a preliminary study to demonstrate localization of [14C]FIAU in tumored mice pretreated with Salmonella expressing HSV1-TK. The [14C]FIAU radioactivity and bacterial count data strongly support a SalmonellaTK-dependent [14C]FIAU accumulation of at least 30-fold higher in tumor tissue compared to muscle tissue. These data warrant further investigation on the use of genetically engineered Salmonella as a systemically administered tumor-specific agents for tumor therapy and delivery of diagnostic imaging markers. © 2001 Elsevier Science B.V. All rights reserved. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; conference paper; drug targeting; cancer diagnosis; neoplasms; mouse; animals; mice; animal tissue; animal experiment; animal model; tumor cell culture; tumor cells, cultured; diagnostic imaging; drug specificity; mice, inbred c57bl; genetic vectors; bacterial protein; drug accumulation; drug distribution; genetic engineering; tissue distribution; device; radioactivity; gene therapy; transgene; arabinofuranosyluracil; reporter gene; drug tissue level; herpesvirus 1, human; protein-tyrosine kinases; radioisotope; neoplasm transplantation; herpes simplex virus 1; genetic markers; hsv1-tk; expression vector; bacterial gene; fiau; virus gene; salmonella typhimurium; salmonella; bacterial count; recombinant dna; priority journal; tumor-targeting; protein hsv1 tk |
| Journal Title: | Journal of Controlled Release |
| Volume: | 74 |
| Issue: | 1-3 |
| ISSN: | 0168-3659 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2001-07-06 |
| Start Page: | 313 |
| End Page: | 315 |
| Language: | English |
| DOI: | 10.1016/s0168-3659(01)00340-6 |
| PUBMED: | 11489512 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Presented at the International Symposium on Tumor Targeted Delivery Systems; 2000 Sep 25-27; Bethesda, MD -- Export Date: 21 May 2015 -- Source: Scopus |
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