Dataset Information

Direct incorporation of the NKT-cell activator ?-galactosylceramide into a recombinant Listeria monocytogenes improves breast cancer vaccine efficacy.

ABSTRACT:

Background

Immune suppression in the tumour microenvironment remains a major limitation to successful immunotherapy of cancer. In the current study, we analysed whether the natural killer T cell-activating glycolipid ?-galactosylceramide could overcome immune suppression and improve vaccination against metastatic breast cancer.

Methods

Mice with metastatic breast cancer (4T1 model) were therapeutically treated with a Listeria monocytogenes-based vaccine expressing tumour-associated antigen Mage-b followed by ?-galactosylceramide as separate agents, or as a complex of ?-galactosylceramide stably incorporated into Listeria-Mage-b. Effects on metastases, tumour weight, toxicity and immune responses were determined.

Results

Sequential treatments of mice with established 4T1 breast carcinomas using Listeria-Mage-b followed by ?-galactosylceramide as a separate agent was highly effective at reducing metastases, but was accompanied by severe liver toxicity. In contrast, combined therapy using Listeria-Mage-b modified by incorporation of ?-galactosylceramide resulted in nearly complete elimination of metastases without toxicity. This was associated with a significant increase in the percentage of natural killer T cells in the spleen, and an increase in natural killer cell activity and in T cell responses to Mage-b.

Conclusions

Our results suggest that direct incorporation of ?-galactosylceramide into a live bacterial vaccine vector is a promising non-toxic new approach for the treatment of metastatic breast cancer.

SUBMITTER: Singh M

PROVIDER: S-EPMC4229631 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Direct incorporation of the NKT-cell activator α-galactosylceramide into a recombinant Listeria monocytogenes improves breast cancer vaccine efficacy.

Singh M M Quispe-Tintaya W W Chandra D D Jahangir A A Venkataswamy M M MM Ng T W TW Sharma-Kharkwal S S Carreño L J LJ Porcelli S A SA Gravekamp C C

British journal of cancer 20141014 10

<h4>Background</h4>Immune suppression in the tumour microenvironment remains a major limitation to successful immunotherapy of cancer. In the current study, we analysed whether the natural killer T cell-activating glycolipid α-galactosylceramide could overcome immune suppression and improve vaccination against metastatic breast cancer.<h4>Methods</h4>Mice with metastatic breast cancer (4T1 model) were therapeutically treated with a Listeria monocytogenes-based vaccine expressing tumour-associate ...[more]

PMID: 25314062

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