Direct incorporation of the NKT-cell activator α-galactosylceramide into a recombinant Listeria monocytogenes improves breast cancer vaccine efficacy
Author
dc.contributor.author
Singh, M.
Author
dc.contributor.author
Quispe-Tintaya, W.
Author
dc.contributor.author
Chandra, D.
Author
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Jahangir, A.
Author
dc.contributor.author
Venkataswamy, M. M.
Author
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Ng, T. W.
Author
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Sharma-Kharkwal, S.
Author
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Carreño, L. J.
Author
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Porcelli, S. A.
Author
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Gravekamp, C.
Admission date
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2019-03-18T11:52:11Z
Available date
dc.date.available
2019-03-18T11:52:11Z
Publication date
dc.date.issued
2014
Cita de ítem
dc.identifier.citation
British Journal of Cancer (2014) 111, 1945–1954
Identifier
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15321827
Identifier
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00070920
Identifier
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10.1038/bjc.2014.486
Identifier
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https://repositorio.uchile.cl/handle/2250/166463
Abstract
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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 a-galactosylceramide could
overcome immune suppression and improve vaccination against metastatic breast cancer.
Abstract
dc.description.abstract
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 a-galactosylceramide as separate agents, or as a complex
of a-galactosylceramide stably incorporated into Listeria-Mage-b. Effects on metastases, tumour weight, toxicity and immune
responses were determined.
Abstract
dc.description.abstract
Results: Sequential treatments of mice with established 4T1 breast carcinomas using Listeria-Mage-b followed by
a-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 a-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.
Abstract
dc.description.abstract
Conclusions: Our results suggest that direct incorporation of a-galactosylceramide into a live bacterial vaccine vector is a
promising non-toxic new approach for the treatment of metastatic breast cancer.