Dendritic cells pulsed with an anti-idiotype antibody mimicking Her-2eu induced protective antitumor immunity in two lines of Her-2eu transgenic mice.

摘要

Her-2eu 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-2eu transgenic mice with 6D12-pulsed dendritic cells (DC) could reverse Her-2eu unresponsiveness and result in the induction of Her-2eu-specific humoral and cellular immune responses and protection against tumors expressing Her-2eu. 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-2eu 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-2eu-specific immune responses. These data suggest the potential use of anti-Id antibody 6D12 as a vaccine for immunotherapy of Her-2eu-positive human cancer.