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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

Inhibition of spontaneous tumor formation by vaccination with virus-like replicon particles (VRP)-neu. Groups of MMTV-c-neu transgenic mice (n = 10 per group) were vaccinated three times (▼) at 2-week intervals with 106 IU VRP-neu (▲) or 106 IU VRP-hemagglutinin (HA) (■). The mice vaccinated with VRP-HA were killed when moribund, and the mice vaccinated with VRP-neu were killed at 240 days.
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Figure 4: Inhibition of spontaneous tumor formation by vaccination with virus-like replicon particles (VRP)-neu. Groups of MMTV-c-neu transgenic mice (n = 10 per group) were vaccinated three times (▼) at 2-week intervals with 106 IU VRP-neu (▲) or 106 IU VRP-hemagglutinin (HA) (■). The mice vaccinated with VRP-HA were killed when moribund, and the mice vaccinated with VRP-neu were killed at 240 days.

Mentions: MMTV-c-neu transgenic mice contain the activated rat neu gene under the control of the MMTV promoter and spontaneously develop neu+ breast tumors within 110–120 days [45]. Without intervention, all of the mice die of breast cancer. We vaccinated groups of mice (n = 10 per group) three times at 14-day intervals with 106 IU VRP-neu or 106 IU VRP-HA and determined the effect on survival. Eight of the 10 mice vaccinated with VRP-HA were killed by 140 days owing to moribundity, and the remaining two mice were killed on day 195 (Fig. 4). None of the mice vaccinated with VRP-neu showed any sign of illness at 240 days, and breast tumors were not evident on palpation. The mice in the VRP-neu-vaccinated group were killed at this time, and gross pathologic examination of the breasts following retraction of the skin did not reveal any tumors. These results demonstrate that vaccination with VRP-neu prevented spontaneous formation of tumor in the breasts of neu transgenic mice and that tolerance to the neu transgene was broken by vaccination with VRP-neu.


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)

Inhibition of spontaneous tumor formation by vaccination with virus-like replicon particles (VRP)-neu. Groups of MMTV-c-neu transgenic mice (n = 10 per group) were vaccinated three times (▼) at 2-week intervals with 106 IU VRP-neu (▲) or 106 IU VRP-hemagglutinin (HA) (■). The mice vaccinated with VRP-HA were killed when moribund, and the mice vaccinated with VRP-neu were killed at 240 days.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Inhibition of spontaneous tumor formation by vaccination with virus-like replicon particles (VRP)-neu. Groups of MMTV-c-neu transgenic mice (n = 10 per group) were vaccinated three times (▼) at 2-week intervals with 106 IU VRP-neu (▲) or 106 IU VRP-hemagglutinin (HA) (■). The mice vaccinated with VRP-HA were killed when moribund, and the mice vaccinated with VRP-neu were killed at 240 days.
Mentions: MMTV-c-neu transgenic mice contain the activated rat neu gene under the control of the MMTV promoter and spontaneously develop neu+ breast tumors within 110–120 days [45]. Without intervention, all of the mice die of breast cancer. We vaccinated groups of mice (n = 10 per group) three times at 14-day intervals with 106 IU VRP-neu or 106 IU VRP-HA and determined the effect on survival. Eight of the 10 mice vaccinated with VRP-HA were killed by 140 days owing to moribundity, and the remaining two mice were killed on day 195 (Fig. 4). None of the mice vaccinated with VRP-neu showed any sign of illness at 240 days, and breast tumors were not evident on palpation. The mice in the VRP-neu-vaccinated group were killed at this time, and gross pathologic examination of the breasts following retraction of the skin did not reveal any tumors. These results demonstrate that vaccination with VRP-neu prevented spontaneous formation of tumor in the breasts of neu transgenic mice and that tolerance to the neu transgene was broken by vaccination with VRP-neu.

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