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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

Protection from tumor challenge after vaccination with virus-like replicon particles (VRP)-neu. Groups of seven or eight mice were vaccinated three times at 2-week intervals with VRP-neu or VRP-hemagglutinin (HA). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad. Five weeks after the tumor challenge, (a) the largest dimension of each tumor was measured and (b) the mice were killed and the mass of the tumor in each animal was determined.
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Figure 2: Protection from tumor challenge after vaccination with virus-like replicon particles (VRP)-neu. Groups of seven or eight mice were vaccinated three times at 2-week intervals with VRP-neu or VRP-hemagglutinin (HA). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad. Five weeks after the tumor challenge, (a) the largest dimension of each tumor was measured and (b) the mice were killed and the mass of the tumor in each animal was determined.

Mentions: Groups of mice (n = 7 per group) were vaccinated subcutaneously with 105 IU or 106 IU VRP-neu or with 106 IU VRP-HA three times at 14-day intervals. Two weeks after the final vaccination, the mice were challenged with 2.5 × 104 A2L2 cells injected into a mammary fat pad. Five weeks after tumor challenge, the largest tumor dimension was measured and the mice were killed. If a tumor was present, its mass was determined. All of the mice vaccinated with VRP-HA had a measurable tumor, whereas only one mouse in each group vaccinated with 106 IU VRP-neu or 105 IU VRP-neu had a measurable tumor (Fig. 2a,2b). These findings clearly demonstrate that vaccination three times with either 105 IU or 106 IU VRP-neu protected mice from challenge with A2L2 cells. VRP-HA failed to provide protection for any of the mice, and therefore the protective effect was specific for the vaccine containing the gene for HER2/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)

Protection from tumor challenge after vaccination with virus-like replicon particles (VRP)-neu. Groups of seven or eight mice were vaccinated three times at 2-week intervals with VRP-neu or VRP-hemagglutinin (HA). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad. Five weeks after the tumor challenge, (a) the largest dimension of each tumor was measured and (b) the mice were killed and the mass of the tumor in each animal was determined.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Protection from tumor challenge after vaccination with virus-like replicon particles (VRP)-neu. Groups of seven or eight mice were vaccinated three times at 2-week intervals with VRP-neu or VRP-hemagglutinin (HA). Two weeks after the final vaccination, the mice were challenged with A2L2 cells injected into a mammary fat pad. Five weeks after the tumor challenge, (a) the largest dimension of each tumor was measured and (b) the mice were killed and the mass of the tumor in each animal was determined.
Mentions: Groups of mice (n = 7 per group) were vaccinated subcutaneously with 105 IU or 106 IU VRP-neu or with 106 IU VRP-HA three times at 14-day intervals. Two weeks after the final vaccination, the mice were challenged with 2.5 × 104 A2L2 cells injected into a mammary fat pad. Five weeks after tumor challenge, the largest tumor dimension was measured and the mice were killed. If a tumor was present, its mass was determined. All of the mice vaccinated with VRP-HA had a measurable tumor, whereas only one mouse in each group vaccinated with 106 IU VRP-neu or 105 IU VRP-neu had a measurable tumor (Fig. 2a,2b). These findings clearly demonstrate that vaccination three times with either 105 IU or 106 IU VRP-neu protected mice from challenge with A2L2 cells. VRP-HA failed to provide protection for any of the mice, and therefore the protective effect was specific for the vaccine containing the gene for HER2/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