TY - JOUR
T1 - Prevention of metastases with a Mage-b DNA vaccine in a mouse breast tumor model
T2 - Potential for breast cancer therapy
AU - Sypniewska, Roza K.
AU - Hoflack, Lieve
AU - Tarango, Melissa
AU - Gauntt, Susan
AU - Leal, Belinda Z.
AU - Reddick, Robert L.
AU - Gravekamp, Claudia
N1 - Funding Information:
We are grateful to Drs. Fred Miller, John Kalns, and Tony Infante for their fruitful discussions and for critical reading of the manuscript, Paul Price for his great assistance in the collection and preparation of tumors and normal tissues, and Mary Robinson for her great assistance in preparing the figures. This work was supported by the American Federation for Aging Research (AFAR) A000106 grant, The Barbara Bowman Award in Cancer Prevention Research from the San Antonio Cancer Institute (SACI), The Helen Freeborn Kerr grant, a National Institute of Aging (NIA) training grant 5T32AG000205-09, and a NIH/NIA RO1 grant (1RO1 AG023096-01).
PY - 2005/5
Y1 - 2005/5
N2 - 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 IFNγ 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.
AB - 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 IFNγ 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.
KW - 4TO7cg model
KW - 64pT model
KW - Breast tumor model
KW - Mage-b DNA vaccine
KW - Metastases
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UR - http://www.scopus.com/inward/citedby.url?scp=18844372588&partnerID=8YFLogxK
U2 - 10.1007/s10549-004-6454-7
DO - 10.1007/s10549-004-6454-7
M3 - Article
C2 - 15868428
AN - SCOPUS:18844372588
SN - 0167-6806
VL - 91
SP - 19
EP - 28
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -
