Anti-tumor activity of an immunotoxin (TGFα-PE38) delivered by attenuated Salmonella typhimurium

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dc.contributor.authorD Lim-
dc.contributor.authorK S Kim-
dc.contributor.authorH J Kim-
dc.contributor.authorKyong-Cheol Ko-
dc.contributor.authorJae Jun Song-
dc.contributor.authorJong Hyun Choi-
dc.contributor.authorM Shin-
dc.contributor.authorJ J Min-
dc.contributor.authorJ H Jeong-
dc.contributor.authorH E Choy-
dc.date.accessioned2017-08-29-
dc.date.available2017-08-29-
dc.date.issued2017-
dc.identifier.issn19492553-
dc.identifier.uri10.18632/oncotarget.17197ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/17193-
dc.description.abstractThe anticancer strategy underlying the use of immunotoxins is as follows: the cancer-binding domain delivers the toxin to a cancer cell, after which the toxin enters and kills the cell. TGFα-PE38 is an immunotoxin comprising transforming growth factor alpha (TGFα), a natural ligand of epidermal growth factor receptor (EGFR), and a modified Pseudomonas exotoxin A (PE38) lacking N terminal cell-binding domain, a highly potent cytotoxic protein moiety. Tumor cells with high level of EGFR undergo apoptosis upon treatment with TGFα-PE38. However, clinical trials demonstrated that this immunotoxin delivered by an intracerebral infusion technique has only a limited inhibitory effect on intracranial tumors mainly due to inconsistent drug delivery. To circumvent this problem, we turned to tumor-seeking bacterial system. Here, we engineered Salmonella typhimurium to selectively express and release TGFα-PE38. Engineered bacteria were administered to mice implanted with mouse colon or breast tumor cells expressing high level of EGFR. We observed that controlled expression and release of TGFα-PE38 from intra-tumoral Salmonellae by either an engineered phage lysis system or by a bacterial membrane transport signal led to significant inhibition of solid tumor growth. These results demonstrated that delivery by tumor-seeking bacteria would greatly augment efficacy of immunotoxin in cancer therapeutics-
dc.publisherImpact Journalsko
dc.titleAnti-tumor activity of an immunotoxin (TGFα-PE38) delivered by attenuated Salmonella typhimurium-
dc.title.alternativeAnti-tumor activity of an immunotoxin (TGFα-PE38) delivered by attenuated Salmonella typhimurium-
dc.typeArticle-
dc.citation.titleOncotarget-
dc.citation.number23-
dc.citation.endPage37560-
dc.citation.startPage37550-
dc.citation.volume8-
dc.contributor.affiliatedAuthorKyong-Cheol Ko-
dc.contributor.affiliatedAuthorJae Jun Song-
dc.contributor.affiliatedAuthorJong Hyun Choi-
dc.contributor.alternativeName임대진-
dc.contributor.alternativeName김광수-
dc.contributor.alternativeName김현주-
dc.contributor.alternativeName고경철-
dc.contributor.alternativeName송재준-
dc.contributor.alternativeName최종현-
dc.contributor.alternativeName신민상-
dc.contributor.alternativeName민정준-
dc.contributor.alternativeName정재호-
dc.contributor.alternativeName최현-
dc.identifier.bibliographicCitationOncotarget, vol. 8, no. 23, pp. 37550-37560-
dc.identifier.doi10.18632/oncotarget.17197-
dc.subject.keywordBacterial cancer therapy-
dc.subject.keywordImmunotoxin-
dc.subject.keywordSalmonella-
dc.subject.keywordTGFα-PE38-
dc.subject.localBacterial cancer therapy-
dc.subject.localImmunotoxin-
dc.subject.localSalmonella-
dc.subject.localTGFα-PE38-
dc.description.journalClassN-
Appears in Collections:
Division of Bio Technology Innovation > SME Support Center > 1. Journal Articles
Jeonbuk Branch Institute > Microbial Biotechnology Research Center > 1. Journal Articles
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