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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

Flow cytometric analysis of A2L2 cells with serum from mice vaccinated with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA). Serum was collected 2 weeks after a single vaccination of Balb/c mice with 106 IU VRP-neu (filled curve) or 106 IU VRP-HA (open curve). The primary serum was diluted with PBS (1:100), and FITC-labeled goat anti-mouse IgG diluted in PBS (1:1000) was used as the secondary antibody.
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Figure 1: Flow cytometric analysis of A2L2 cells with serum from mice vaccinated with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA). Serum was collected 2 weeks after a single vaccination of Balb/c mice with 106 IU VRP-neu (filled curve) or 106 IU VRP-HA (open curve). The primary serum was diluted with PBS (1:100), and FITC-labeled goat anti-mouse IgG diluted in PBS (1:1000) was used as the secondary antibody.

Mentions: Groups of Balb/c mice (n = 5 per group) were vaccinated once subcutaneously in one hind leg footpad with either 106 IU VRP-neu or 106 IU VRP-HA suspended in PBS. The HER2/neu-specific humoral response of serum pooled from mice in each group was measured 14 days later by flow cytometry using A2L2 cells. Compared with the mice vaccinated with VRP-HA, the mice vaccinated with VRP-neu had a strong IgG response (Fig. 1). Pre-immune sera for both groups were nonreactive with A2L2 cells, and immune sera from both vaccinated groups were nonreactive with 66.3 cells, the parental cell line from which A2L2 was derived by transfection with neu (data not shown).


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)

Flow cytometric analysis of A2L2 cells with serum from mice vaccinated with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA). Serum was collected 2 weeks after a single vaccination of Balb/c mice with 106 IU VRP-neu (filled curve) or 106 IU VRP-HA (open curve). The primary serum was diluted with PBS (1:100), and FITC-labeled goat anti-mouse IgG diluted in PBS (1:1000) was used as the secondary antibody.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Flow cytometric analysis of A2L2 cells with serum from mice vaccinated with virus-like replicon particles (VRP)-neu or VRP-hemagglutinin (HA). Serum was collected 2 weeks after a single vaccination of Balb/c mice with 106 IU VRP-neu (filled curve) or 106 IU VRP-HA (open curve). The primary serum was diluted with PBS (1:100), and FITC-labeled goat anti-mouse IgG diluted in PBS (1:1000) was used as the secondary antibody.
Mentions: Groups of Balb/c mice (n = 5 per group) were vaccinated once subcutaneously in one hind leg footpad with either 106 IU VRP-neu or 106 IU VRP-HA suspended in PBS. The HER2/neu-specific humoral response of serum pooled from mice in each group was measured 14 days later by flow cytometry using A2L2 cells. Compared with the mice vaccinated with VRP-HA, the mice vaccinated with VRP-neu had a strong IgG response (Fig. 1). Pre-immune sera for both groups were nonreactive with A2L2 cells, and immune sera from both vaccinated groups were nonreactive with 66.3 cells, the parental cell line from which A2L2 was derived by transfection with neu (data not shown).

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