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J Cancer Res Clin Oncol. 2008 May;134(5):525-33. Epub 2007 Oct 2.

Enhancement of dendritic cell-tumor fusion vaccine potency by indoleamine-pyrrole 2,3-dioxygenase inhibitor, 1-MT.

Author information

1
Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, 74 Zhongshan Road, Guangzhou 510080, China.

Abstract

PURPOSE:

Dendritic cell (DC)-based cancer vaccines are currently being evaluated as novel anti-tumor vaccination strategies, but in some cases, they are demonstrated to have poor clinical efficacies than anticipated. A potential reason is immune tolerance due to the immunosuppressive enzyme, indoleamine-pyrrole 2,3-dioxygenase (IDO). The aim of this study was to determine whether blocking the activity of IDO might improve the anti-tumor efficacy of DC/Lewis lung carcinoma (LLC) fusion vaccine applied to the mouse LLC model.

METHODS:

To prepare the DC/LLC fusion vaccine, DCs were fused with LLC using polyethylene glycol (PEG) as described. The IDO expression in the DC/LLC fusion vaccine and in the vaccinated mice was detected by western blot (WB) and/or immunohistochemical (IHC) analysis. This fusion vaccine, as a single agent or in combination with 1-methyl-tryptophan (1-MT, an IDO inhibitor), was administered to LLC mice. The anti-tumor efficacy in different treatment was determined by regular observation of tumor development and the level of splenic cytotoxic T lymphocyte (CTL) response, which was examined by lactate dehydrogenase (LDH) release.

RESULTS:

In the LLC mice, we observed that IDO-positive cells were extensively accumulated in tumor draining lymph nodes (TDLNs). Furthermore, WB and IHC analysis results showed that vaccination with fusion DC/LLC cells alone caused significant up-regulation of IDO in spleens. 1-MT enhanced the anti-tumor efficacy elicited by DC/LLC fusion vaccine via delaying the tumor development and inducing stronger splenic CTL responses.

CONCLUSIONS:

Our results indicate an IDO-mediated immunosuppressive mechanism might be involved in weakening the anti-tumor efficacy elicited by DC/LLC fusion vaccine, and specific inhibition of IDO activity might be required for development of cancer vaccines.

PMID:
17909857
DOI:
10.1007/s00432-007-0315-9
[Indexed for MEDLINE]

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