Targeting HER-2/neu for active-specific immunotherapy in a mouse model of spontaneous breast cancer.
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.
Céfaï
D
D
Department of Clinical Research, University of Bern, Bern, Switzerland.
Morrison
B W
BW
Sckell
A
A
Favre
L
L
Balli
M
M
Leunig
M
M
Gimmi
C D
CD
D016475:3T3 Cells; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D017252:CD3 Complex / Q000032:analysis; D005260:Female; D006084:Graft Rejection; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D000912:Antibodies, Neoplasm; D017252:CD3 Complex; D018719:Erb-b2 Receptor Tyrosine Kinases