Her-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. To test the efficacy of immune-based strategies in eliciting an antitumor response, we have evaluated the vaccine potential of an anti-idiotype (Id) antibody, 6D12 in tolerant hosts. Immunization of human Her-2/neu transgenic mice with 6D12-pulsed dendritic cells (DC) could reverse Her-2/neu unresponsiveness and result in the induction of Her-2/neu-specific humoral and cellular immune responses and protection against tumors expressing Her-2/neu. Furthermore, the tumor rejection in 6D12-pulsed DC immunized mice was associated with development of memory response. Vaccination of transgenic female FVB-neuN mice that carry the rat Her-2/neu oncogene, markedly delayed tumor onset and developed significantly fewer spontaneous mammary tumors compared with mice treated with control vaccine. Tumor growth inhibition was associated with the induction of Her-2/neu-specific immune responses. These data suggest the potential use of anti-Id antibody 6D12 as a vaccine for immunotherapy of Her-2/neu-positive human cancer.
Bibliographical noteFunding Information:
We thank Dr. Wei-Zen Wei (Karmanos Cancer Institute, Wayne State University, Detroit, Michigan) for providing human Her-2/neu transgenic breeder mice, David Ginsburg for excellent assistance in animal studies, and Mary B. Palascak for help in flow cytometry. This work was supported by the NIH Grant RO1 CA91878.
- Anti-idiotype antibody
- Antitumor immunity
- Breast cancer
- Transgenic mice