TY - JOUR
T1 - A new immunization and treatment strategy for mouse mammary tumor virus (MMTV) associated cancers
AU - Braitbard, Ori
AU - Roniger, Maayan
AU - Bar-Sinai, Allan
AU - Rajchman, Dana
AU - Gross, Tamar
AU - Abramovitch, Hillel
AU - La Ferla, Marco
AU - Franceschi, Sara
AU - Lessi, Francesca
AU - Naccarato, Antonio Giuseppe
AU - Mazzanti, Chiara M.
AU - Bevilacqua, Generoso
AU - Hochman, Jacob
PY - 2016/4/19
Y1 - 2016/4/19
N2 - Mouse Mammary Tumor Virus (MMTV) causes mammary carcinoma or lymphoma in mice. An increasing body of evidence in recent years supports its involvement also in human sporadic breast cancer. It is thus of importance to develop new strategies to impair the development, growth and metastasis of MMTV-associated cancers. The signal peptide of the envelope precursor protein of this virus: MMTV-p14 (p14) is an excellent target for such strategies, due to unique characteristics distinct from its regular endoplasmic reticulum targeting function. These include cell surface expression in: Murine cancer cells that harbor the virus, human breast cancer (MCF-7) cells that ectopically express p14, as well as cultured human cells derived from an invasive ductal breast carcinoma positive for MMTV sequences. These findings support its use in signal peptide-based immune targeting. Indeed, priming and boosting mice with p14 elicits a specific anti-signal peptide immune response sufficient for protective vaccination against MMTV-associated tumors. Furthermore, passive immunization using a combination of anti-p14 monoclonal antibodies or the transfer of T-cells from immunized mice (Adoptive Cell Transfer) is also therapeutically effective. With reports demonstrating involvement of MMTV in human breast cancer, we propose the immune-mediated targeting of p14 as a strategy for prevention, treatment and diagnosis of MMTV-associated cancers.
AB - Mouse Mammary Tumor Virus (MMTV) causes mammary carcinoma or lymphoma in mice. An increasing body of evidence in recent years supports its involvement also in human sporadic breast cancer. It is thus of importance to develop new strategies to impair the development, growth and metastasis of MMTV-associated cancers. The signal peptide of the envelope precursor protein of this virus: MMTV-p14 (p14) is an excellent target for such strategies, due to unique characteristics distinct from its regular endoplasmic reticulum targeting function. These include cell surface expression in: Murine cancer cells that harbor the virus, human breast cancer (MCF-7) cells that ectopically express p14, as well as cultured human cells derived from an invasive ductal breast carcinoma positive for MMTV sequences. These findings support its use in signal peptide-based immune targeting. Indeed, priming and boosting mice with p14 elicits a specific anti-signal peptide immune response sufficient for protective vaccination against MMTV-associated tumors. Furthermore, passive immunization using a combination of anti-p14 monoclonal antibodies or the transfer of T-cells from immunized mice (Adoptive Cell Transfer) is also therapeutically effective. With reports demonstrating involvement of MMTV in human breast cancer, we propose the immune-mediated targeting of p14 as a strategy for prevention, treatment and diagnosis of MMTV-associated cancers.
KW - Adoptive cell transfer
KW - Breast cancer
KW - Monoclonal antibodies
KW - Mouse mammary tumor virus
KW - Pathology Section
KW - Signal peptide
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=84965043329&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7762
DO - 10.18632/oncotarget.7762
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C2 - 26934560
AN - SCOPUS:84965043329
SN - 1949-2553
VL - 7
SP - 21168
EP - 21180
JO - Oncotarget
JF - Oncotarget
IS - 16
ER -
