title: Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases.
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.
authors: California Pacific Medical Center Research Institute, 475 Brannan Street, San Francisco, CA 94107, USA.
authors: S H
authors: SH
authors: Kim
authors: F
authors: F
authors: Castro
authors: D
authors: D
authors: Gonzalez
authors: P C
authors: PC
authors: Maciag
authors: Y
authors: Y
authors: Paterson
authors: C
authors: C
authors: Gravekamp
mesh_terms: 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
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D017931:DNA Primers; C489518:Mageb1 protein, mouse; C512965:Mageb2 protein, mouse; D009363:Neoplasm Proteins