Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases.
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.
Kim
S H
SH
California Pacific Medical Center Research Institute, 475 Brannan Street, San Francisco, CA 94107, USA.
Castro
F
F
Gonzalez
D
D
Maciag
P C
PC
Paterson
Y
Y
Gravekamp
C
C
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D008089:Listeria monocytogenes / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D017931:DNA Primers; C489518:Mageb1 protein, mouse; C512965:Mageb2 protein, mouse; D009363:Neoplasm Proteins