Signal peptides (SPs) are N-terminal extensions on nascent secretory and membrane proteins that mediate insertion into, or translocation across the membrane of the endoplasmic reticulum (ER). A growing number of SPs have been shown to carry out post-ER targeting functions. A case in point is the SP of the envelope precursor protein of Mouse Mammary Tumor Virus (MMTV), a beta retrovirus known to cause lymphoma and mammry carcinoma in laboratory mice. This signal peptide (named MMTV-p14 , or p14 for short) is uniquely localized to nucleoli of cells that harbor the virus where it binds to specific protein targets and functions as a nuclear export factor for viral transcripts. P14 is also a phosphoprotein tumor modulator, the phosphorylation status of which determines whether it will function, in vivo, in a tumor promoting or tumor suppressing capacity.
Here we report that p14 is expressed also on the surface of a variety of cells that contain MMTV (murine lymphoma and mammary carcinoma, and human breast cancer cells ectopically expressing p14). Furthermore p14 is immunogenic and vaccination with purified recombinant p14 (using different adjuvants) is sufficient to immunize mice against malignant cells that harbor MMTV. This can be adoptively transferred into naïve mice.
Furthermore, newly derived monoclonal anti-p14 antibodies with different epitope specificity are now available to study their effect on MMTV associated tumors in vivo as well as for targeted drug delivery to these tumors
In view of reports suggesting involvement of MMTV in about 30% of human breast cancers we propose p14 and anti-p14 antibodies as candidates for immunization against MMTV associated malignancies, and as a functional example for other viral signal peptides.
Citation Format: Ori Braitbard, Tamar Gross, Maayan Roniger, Allan Bar-Sinai, Nira Hochman, Jacob Hochman. Signal peptide –mediated immunization against mouse mammary tumor virus (MMTV)-associated tumors. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B30.
- ©2015 American Association for Cancer Research.