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Targeting HER‐2/neu for active‐specific immunotherapy in a mouse model of spontaneous breast cancer
Author(s) -
Céfaï Daniel,
Morrison Briggs W.,
Sckell Axel,
Favre Luc,
Balli Marietta,
Leunig Michael,
Gimmi Claude D.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19991029)83:3<393::aid-ijc16>3.0.co;2-m
Subject(s) - immune system , immunotherapy , active immunotherapy , antigen , immunology , breast cancer , vaccination , cancer immunotherapy , cancer research , cancer , medicine , biology
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.