Targeting HER‐2/neu for active‐specific immunotherapy in a mouse model of spontaneous breast cancer

• Published in: International journal of cancer 1999-10, Vol.83 (3), p.393-400
• Main Authors: Céfaï, Daniel, Morrison, Briggs W., Sckell, Axel, Favre, Luc, Balli, Marietta, Leunig, Michael, Gimmi, Claude D.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Antibodies, Neoplasm - biosynthesis; Biological and medical sciences; CD3 Complex - analysis; Female; Graft Rejection; HER-2 gene; Mammary Neoplasms, Animal - prevention & control; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Transgenic; neu gene; Other treatments; Receptor, ErbB-2 - immunology; T-Lymphocytes - immunology; Treatment. General aspects; Tumors; Vaccination
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19991029)83:3<393::AID-IJC16>3.0.CO;2-M

The identification of tumor‐associated antigens has led to increased interest in vaccination strategies to treat and/or prevent cancer. This study examined the feasibility of active‐specific immunotherapy against the breast‐tumor antigen HER‐2/neu using a HER‐2/neu transgenic (rNeu‐TG) mouse model. rNeu‐TG mice develop spontaneous breast tumors after pregnancy, indicating that they fail to mount an effective immune response against rNeu. Allogeneic fibroblasts expressing HER‐2/neu were used as a cell‐based vaccine. Vaccination induced a rNeu‐specific anti‐tumor immune response that prevented tumor formation of transplanted breast‐tumor cells, and also protected mice from spontaneous tumor formation. Both T‐cell‐mediated and humoral immune responses were detectable in vaccinated mice. Vaccination also protected tumor‐bearing mice from a challenge with cell suspensions isolated from spontaneous tumors, indicating that rNeu‐TG mice are not tolerant to rNeu, even after spontaneous tumor formation. However, established spontaneous tumors themselves were never affected. This observation correlated with T‐cell infiltrations in the injected but not in the established spontaneous tumor. Thus, allogeneic fibroblasts are efficient vaccine vectors to prime a specific immune response against an over‐expressed tumor antigen. Moreover, our results suggest striking differences in the immunological requirements for the rejection of an established vs. a transplanted tumor. Int. J. Cancer 83:393–400, 1999. © 1999 Wiley‐Liss, Inc.