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- Title
Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases.
- Authors
Kim, S. H.; Castro, F.; Gonzalez, D.; Maciag, P. C.; Paterson, Y.; Gravekamp, C.
- Abstract
New therapies are needed that target breast cancer metastases. In previous studies, we have shown that vaccination with pcDNA3.1-Mage-b DNA vaccine is effective against breast cancer metastases. In the study presented here, we have further enhanced the efficacy of Mage-b vaccination through the improved delivery of the vaccine using recombinant Listeria monocytogenes (LM). Three overlapping fragments of Mage-b as well as the complete protein-encoding region of Mage-b have been expressed as a fusion protein with a truncated non-cytolytic form of listeriolysin O (LLO) in recombinant LM. These different Mage-b vaccine strains were preventively tested for their efficacy against breast cancer metastases in a syngeneic mouse tumour model 4T1. The LM-LLO-Mage-b/2nd, expressing position 311-660 of the cDNA of Mage-b, was the most effective vaccine strain against metastases in the 4T1 mouse breast tumour model. Vaccination with LM-LLO-Mage-b/2nd dramatically reduced the number of metastases by 96% compared with the saline group and by 88% compared with the vector control group (LM-LLO), and this correlated with strong Mage-b-specific CD8 T-cell responses in the spleen, after restimulation with Mage-b. However, no effect of LM-LLO-Mage-b/2nd was observed on 4T1 primary tumours, which may be the result of a complete absence of Mage-b-specific immune responses in the draining lymph nodes. Vaccination with LM-LLO-Mage-b/2nd could be an excellent follow-up after removal of the primary tumour, to eliminate metastases and residual tumour cells.
- Subjects
LISTERIA monocytogenes; BREAST cancer vaccines; BREAST cancer treatment; METASTASIS; DNA vaccines; TUMORS; VECTOR control; THERAPEUTICS; BREAST tumor treatment; ANIMAL experimentation; BREAST tumors; CELL lines; DNA probes; GENETICS; LISTERIA; MICE; NUCLEOTIDES; POLYMERASE chain reaction; PROTEINS; RESEARCH funding; TUMOR antigens; CANCER vaccines; TREATMENT effectiveness; REVERSE transcriptase polymerase chain reaction; VACCINES
- Publication
British Journal of Cancer, 2008, Vol 99, Issue 5, p741
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6604526