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Targeting HER-2/neu for active-specific immunotherapy in a mouse model of spontaneous breast cancer
D Céfaï1, B W Morrison, A Sckell
1Department of Clinical Research, University of Bern, Bern, Switzerland.
Abstract:
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.
Insights
Active-specific immunotherapy using HER-2/neu-expressing fibroblasts prevented tumor formation in mice. This approach successfully primed anti-tumor immune responses, highlighting potential for cancer vaccination strategies.
Area of Science:
- Immunology
- Oncology
- Vaccine Development
Background:
- Tumor-associated antigens are key targets for cancer immunotherapy.
- HER-2/neu is a significant antigen in breast cancer.
- Transgenic mouse models are crucial for studying anti-tumor immunity.
Purpose of the Study:
- To evaluate active-specific immunotherapy against the HER-2/neu antigen in a relevant mouse model.
- To assess the efficacy of allogeneic fibroblasts as vaccine vectors.
- To investigate the immune response to HER-2/neu in preventing and treating breast tumors.
Main Methods:
- Utilized a HER-2/neu transgenic (rNeu-TG) mouse model that spontaneously develops breast tumors.
- Administered allogeneic fibroblasts engineered to express HER-2/neu as a cell-based vaccine.
- Assessed tumor prevention, immune response (T-cell and humoral), and therapeutic potential against transplanted and spontaneous tumors.
Main Results:
- Vaccination with HER-2/neu-expressing fibroblasts successfully prevented transplanted and spontaneous tumor formation.
- Induced robust HER-2/neu-specific T-cell-mediated and humoral immune responses.
- Demonstrated that vaccinated mice rejected transplanted tumors and resisted spontaneous tumor development.
- Showed that established spontaneous tumors were unaffected, correlating with limited T-cell infiltration.
Conclusions:
- Allogeneic fibroblasts serve as effective vaccine vectors for eliciting specific anti-tumor immunity against over-expressed antigens like HER-2/neu.
- The study highlights distinct immunological requirements for rejecting transplanted versus established tumors.
- Results suggest potential for fibroblast-based vaccines in preventing cancer, but challenges remain for treating established disease.
