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 w a transplanted tumor.