Prevention of metastases with a Mage-b DNA vaccine in a mouse breast tumor model: potential for breast cancer therapy.
Anti-tumor vaccines are a relatively non-toxic alternative to conventional chemotherapeutic strategies to control breast cancer. Immunization with tumor-associated antigens (TAAs) triggers anti-tumor cytotoxic T lymphocytes (CTL), which can limit tumor progression. Here we report on the development and effectiveness of a TAA-based DNA vaccine encoding Mage-b1/2, the mouse homologue of the human MAGE-B1/2. As model system, we used immune competent Balb/c mice with syngeneic non-metastatic (64pT) or metastatic (4TO7cg) breast tumors. First, the presence of Mage-btranscripts in the 64pT and 4TO7cg breast tumors and metastases was demonstrated by RT-PCR, Southern blotting, and DNA sequencing. A DNA-based vaccine was developed from transcripts of one of the 64pT tumors, encoding the complete Mage-b1/2 protein, and subsequently tested for its preventive efficacy in both breast tumor models. Mice were immunized two times intramuscularly with the vaccine (pcDNA3.1-Mage-b1/2-V5), the control vector (pcDNA3.1-V5), or saline. Two weeks after the last immunization, the syngeneic 4TO7cg or 64pT tumor cell lines were injected in a mammary fat pad. Mice were monitored during the next 4 weeks for tumor formation, latency and size, and subsequently sacrificed for analysis. While the Mage-b1/2 vaccine had only a minor effect on the latency and growth of primary tumors, a significant and reproducible reduction in the number of 4TO7cg metastases was observed (vaccine versus control vector, p=0.0329; vaccine versus saline, p=0.0128). The observed protective efficacy of the Mage-b DNA vaccine correlated with high levels of vaccine-induced IFNgamma in spleen and lymph nodes upon re-stimulation in vitro. These results demonstrate the potential of TAA-based DNA vaccines in controlling metastatic disease in breast cancer patients.
Sypniewska
Roza K
RK
Department of Cellular and Structural Biology, University of Texas Health Science Center, STCBM building, 15355 Lambda Drive, San Antonio, TX 78245, USA.
Hoflack
Lieve
L
Tarango
Melissa
M
Gauntt
Susan
S
Leal
Belinda Z
BZ
Reddick
Robert L
RL
Gravekamp
Claudia
C
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000662:veterinary; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C097488:MAGEB1 protein, human; C512965:Mageb2 protein, mouse; D009363:Neoplasm Proteins; D019444:Vaccines, DNA