Lani
10-23-2007, 04:58 AM
Clin Cancer Res. 2007 Oct 15;13(20):6195-203.
Antibody and CD8+ T Cell Responses against HER2/neu Required for Tumor Eradication after DNA Immunization with a Flt-3 Ligand Fusion Vaccine.
Orlandi F, Venanzi FM, Concetti A, Yamauchi H, Tiwari S, Norton L, Wolchok JD, Houghton AN, Gregor PD.
Authors' Affiliations: Swim Across America Laboratory. Memorial Sloan-Kettering Cancer Center, New York, New York; and Unit of Translational Medicine. University of Camerino, Camerino (MC), Italy.
PURPOSE: HER2/neu is frequently overexpressed in breast cancer. In a mouse model, vaccination with HER2/neu DNA elicits antibodies that confer partial protection against tumor challenge. EXPERIMENTAL DESIGN: To enhance antitumor immunity, we fused cDNA encoding Flt-3 ligand (FL) to the rat HER2/neu extracellular domain (neu), generating a chimeric FLneu molecule. FLneu and neu DNA vaccines were compared for immunogenicity and their ability to protect mice from tumor challenge. RESULTS: The neu vaccine generated a HER2/neu-specific antibody response. In contrast, vaccination with FLneu induced CD8(+) T cells specific for HER2/neu but a negligible anti-HER2/neu antibody response. The switch from an antibody-mediated to T cell-mediated response was due to different intracellular localization of neu and FLneu. Although the neu protein was secreted, the FLneu protein was retained inside the cell, co-localizing with the endoplasmic reticulum, facilitating processing and presentation to T cells. The neu and FLneu vaccines individually conferred only weak tumor immunity. However, efficient tumor rejection was seen when neu and FLneu were combined, inducing both strong anti-HER2/neu-specific antibody and T cell responses. Adoptive transfer of both immune CD8(+) T cells and immune sera from immunized mice was required to confer tumor immunity in naïve hosts. CONCLUSIONS: These results show that active induction of both humoral and cellular immunity to HER2/neu is required for efficient tumor protection, and that neither response alone is sufficient.
PMID: 17947487 [PubMed - in process]
Translation--by combining the raisiing of both kinds of immunity, humoral and cellular they wer able to get the vaccine to protect against her2neu-type breast cancer in the mouse
Antibody and CD8+ T Cell Responses against HER2/neu Required for Tumor Eradication after DNA Immunization with a Flt-3 Ligand Fusion Vaccine.
Orlandi F, Venanzi FM, Concetti A, Yamauchi H, Tiwari S, Norton L, Wolchok JD, Houghton AN, Gregor PD.
Authors' Affiliations: Swim Across America Laboratory. Memorial Sloan-Kettering Cancer Center, New York, New York; and Unit of Translational Medicine. University of Camerino, Camerino (MC), Italy.
PURPOSE: HER2/neu is frequently overexpressed in breast cancer. In a mouse model, vaccination with HER2/neu DNA elicits antibodies that confer partial protection against tumor challenge. EXPERIMENTAL DESIGN: To enhance antitumor immunity, we fused cDNA encoding Flt-3 ligand (FL) to the rat HER2/neu extracellular domain (neu), generating a chimeric FLneu molecule. FLneu and neu DNA vaccines were compared for immunogenicity and their ability to protect mice from tumor challenge. RESULTS: The neu vaccine generated a HER2/neu-specific antibody response. In contrast, vaccination with FLneu induced CD8(+) T cells specific for HER2/neu but a negligible anti-HER2/neu antibody response. The switch from an antibody-mediated to T cell-mediated response was due to different intracellular localization of neu and FLneu. Although the neu protein was secreted, the FLneu protein was retained inside the cell, co-localizing with the endoplasmic reticulum, facilitating processing and presentation to T cells. The neu and FLneu vaccines individually conferred only weak tumor immunity. However, efficient tumor rejection was seen when neu and FLneu were combined, inducing both strong anti-HER2/neu-specific antibody and T cell responses. Adoptive transfer of both immune CD8(+) T cells and immune sera from immunized mice was required to confer tumor immunity in naïve hosts. CONCLUSIONS: These results show that active induction of both humoral and cellular immunity to HER2/neu is required for efficient tumor protection, and that neither response alone is sufficient.
PMID: 17947487 [PubMed - in process]
Translation--by combining the raisiing of both kinds of immunity, humoral and cellular they wer able to get the vaccine to protect against her2neu-type breast cancer in the mouse