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

M. Singh, W. Quispe-Tintaya, D. Chandra, A. Jahangir, M. M. Venkataswamy, Tony W. Ng, Shalu Sharma, L. J. Carreño, Steven A. Porcelli, Claudia Gravekamp

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 α-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 α-galactosylceramide as separate agents, or as a complex of α-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 α-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 α-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 α-galactosylceramide into a live bacterial vaccine vector is a promising non-toxic new approach for the treatment of metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)1945-1954
Number of pages10
JournalBritish Journal of Cancer
Volume111
Issue number10
DOIs
StatePublished - Nov 11 2014

Fingerprint

Galactosylceramides
Cancer Vaccines
Natural Killer T-Cells
Listeria monocytogenes
Breast Neoplasms
Listeria
Neoplasm Metastasis
Bacterial Vaccines
Tumor Microenvironment
Glycolipids
Neoplasm Antigens
Tumor Burden
Natural Killer Cells
Immunotherapy
Vaccination
Therapeutics
Vaccines
Spleen
T-Lymphocytes
Liver

Keywords

  • a-galactosylceramide
  • breast cancer
  • Listeria monocytogenes
  • metastases
  • NKT cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Direct incorporation of the NKT-cell activator α-galactosylceramide into a recombinant Listeria monocytogenes improves breast cancer vaccine efficacy. / Singh, M.; Quispe-Tintaya, W.; Chandra, D.; Jahangir, A.; Venkataswamy, M. M.; Ng, Tony W.; Sharma, Shalu; Carreño, L. J.; Porcelli, Steven A.; Gravekamp, Claudia.

In: British Journal of Cancer, Vol. 111, No. 10, 11.11.2014, p. 1945-1954.

Research output: Contribution to journalArticle

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