title: A new immunization and treatment strategy for mouse mammary tumor virus (MMTV) associated cancers.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Braitbard
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Roniger
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Allan
authors.initials: A
authors.lastname: Bar-Sinai
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Rajchman
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Gross
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Hillel
authors.initials: H
authors.lastname: Abramovitch
authors.affiliation: FPS - Pisa Science Foundation, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: La Ferla
authors.affiliation: FPS - Pisa Science Foundation, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Franceschi
authors.affiliation: FPS - Pisa Science Foundation, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lessi
authors.affiliation: Department of Pathology, University of Pisa, Pisa, Italy.
authors.forename: Antonio Giuseppe
authors.initials: AG
authors.lastname: Naccarato
authors.affiliation: FPS - Pisa Science Foundation, Pisa, Italy.
authors.forename: Chiara M
authors.initials: CM
authors.lastname: Mazzanti
authors.affiliation: FPS - Pisa Science Foundation, Pisa, Italy.|Department of Pathology, University of Pisa, Pisa, Italy.
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hochman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018270:Carcinoma, Ductal, Breast / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D061986:MCF-7 Cells; D008324:Mammary Tumor Virus, Mouse / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014759:Viral Envelope Proteins
keywords: Pathology Section; adoptive cell transfer; breast cancer; monoclonal antibodies; mouse mammary tumor virus; signal peptide; vaccine