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Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis.

Wang X, Wang JP, Maughan MF, Lachman LB - Breast Cancer Res. (2004)

Bottom Line: Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective.Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model.Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. xywang@mdanderson

ABSTRACT

Introduction: Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective.

Methods: Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model.

Results: VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG.

Conclusion: On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu+ breast cancer is warranted.

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Related in: MedlinePlus

Minimal effective vaccine dose in two tumor prevention models. Groups of four or five mice were vaccinated once, twice or three times (1X, 2X, or 3X) at 2-week intervals with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA) (104 IU or 105 IU). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad or intravensouly. The mice were killed 5 weeks after the tumor challenge. (a) The mass of the mammary tumors, if present, was determined in the mammary fat pad prevention model group, and (b) the number of surface metastases on the lungs was determined in the experimental lung metastasis prevention model group.
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Figure 3: Minimal effective vaccine dose in two tumor prevention models. Groups of four or five mice were vaccinated once, twice or three times (1X, 2X, or 3X) at 2-week intervals with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA) (104 IU or 105 IU). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad or intravensouly. The mice were killed 5 weeks after the tumor challenge. (a) The mass of the mammary tumors, if present, was determined in the mammary fat pad prevention model group, and (b) the number of surface metastases on the lungs was determined in the experimental lung metastasis prevention model group.

Mentions: Because vaccination three times with 105 IU VRP-neu prevented tumor growth in a mammary fat pad, we next determined the minimum number of VRP-neu particles and the minimum number of vaccinations necessary to significantly inhibit tumor growth. In the mammary fat pad prevention model, vaccination twice with 105 IU VRP-neu or vaccination three times with 104 IU VRP-neu completely prevented tumor growth in many mice and significantly reduced the tumor mass in the entire group compared with the tumor mass of the mice vaccinated three times with VRP-HA (Fig. 3a). Identical results were obtained in the experimental lung metastasis prevention model, in which mice were injected with A2L2 cells intravenously in the tail vein after vaccination (Fig. 3b). These results demonstrate that, in both tumor models, vaccination three times with 104 IU VRP-neu or twice with 105 IU VRP-neu significantly reduced the tumor mass and lung metastasis. In addition, several mice in each vaccinated group were tumor free in mammary tissue or lungs.


Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis.

Wang X, Wang JP, Maughan MF, Lachman LB - Breast Cancer Res. (2004)

Minimal effective vaccine dose in two tumor prevention models. Groups of four or five mice were vaccinated once, twice or three times (1X, 2X, or 3X) at 2-week intervals with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA) (104 IU or 105 IU). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad or intravensouly. The mice were killed 5 weeks after the tumor challenge. (a) The mass of the mammary tumors, if present, was determined in the mammary fat pad prevention model group, and (b) the number of surface metastases on the lungs was determined in the experimental lung metastasis prevention model group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064108&req=5

Figure 3: Minimal effective vaccine dose in two tumor prevention models. Groups of four or five mice were vaccinated once, twice or three times (1X, 2X, or 3X) at 2-week intervals with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA) (104 IU or 105 IU). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad or intravensouly. The mice were killed 5 weeks after the tumor challenge. (a) The mass of the mammary tumors, if present, was determined in the mammary fat pad prevention model group, and (b) the number of surface metastases on the lungs was determined in the experimental lung metastasis prevention model group.
Mentions: Because vaccination three times with 105 IU VRP-neu prevented tumor growth in a mammary fat pad, we next determined the minimum number of VRP-neu particles and the minimum number of vaccinations necessary to significantly inhibit tumor growth. In the mammary fat pad prevention model, vaccination twice with 105 IU VRP-neu or vaccination three times with 104 IU VRP-neu completely prevented tumor growth in many mice and significantly reduced the tumor mass in the entire group compared with the tumor mass of the mice vaccinated three times with VRP-HA (Fig. 3a). Identical results were obtained in the experimental lung metastasis prevention model, in which mice were injected with A2L2 cells intravenously in the tail vein after vaccination (Fig. 3b). These results demonstrate that, in both tumor models, vaccination three times with 104 IU VRP-neu or twice with 105 IU VRP-neu significantly reduced the tumor mass and lung metastasis. In addition, several mice in each vaccinated group were tumor free in mammary tissue or lungs.

Bottom Line: Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective.Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model.Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. xywang@mdanderson

ABSTRACT

Introduction: Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective.

Methods: Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model.

Results: VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG.

Conclusion: On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu+ breast cancer is warranted.

Show MeSH
Related in: MedlinePlus