TY - JOUR
T1 - Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases
AU - Kim, S. H.
AU - Castro, F.
AU - Gonzalez, D.
AU - Maciag, P. C.
AU - Paterson, Y.
AU - Gravekamp, C.
N1 - Funding Information:
We thank Dr ZhenHang Meng for the pathological analysis of the mouse tissues, and Sue Louiseau for editing the manuscript. This work was supported by NIA Grant 1RO1 AG023096-01 and the American Federation for Aging Research (AFAR) A000106.
PY - 2008/9/2
Y1 - 2008/9/2
N2 - 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.
AB - 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.
KW - 4T1 model
KW - Breast cancer metastases
KW - Listeria monocytogenes
KW - Mage-b DNA vaccine
UR - http://www.scopus.com/inward/record.url?scp=50249100180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50249100180&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6604526
DO - 10.1038/sj.bjc.6604526
M3 - Article
C2 - 18728665
AN - SCOPUS:50249100180
SN - 0007-0920
VL - 99
SP - 741
EP - 749
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -