Immunoprevention of HER-2/<b>
                     <i>neu</i>
                  </b> Transgenic Mammary Carcinoma through an Interleukin 12-Engineered Allogeneic Cell Vaccine

Giovanni, Carla De; Nicoletti, Giordano; Landuzzi, Lorena; Astolfi, Annalisa; Croci, Stefania; Comes, Alberto; Ferrini, Silvano; Meazza, Raffaella; Iezzi, Manuela; Carlo, Emma Di; Musiani, Piero; Cavallo, Federica; Nanni, Patrizia; Lollini, Pier‐Luigi

doi:10.1158/0008-5472.can-03-2984

Cited by 78 publications

(88 citation statements)

References 43 publications

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“…3 Among the various immunopreventive approaches performed on HER-2/neu models, 4 -12 vaccination with allogeneic mammary carcinoma cells expressing HER-2/neu combined with interleukin (IL)-12 is able to reach a striking percentage of long-term protection from mammary carcinoma development, maintaining 90 to 100% of mice free from tumor up to at least 1 year of age. 13,14 Molecular analysis of the immune response in the mammary gland environment and of changes in the tumor genetic program induced by vaccination would improve the design of new immunopreventive approaches by revealing the gene expression signature of both the achievement and the failure of the immune protection from tumor development.…”

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confidence: 99%

Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma

Astolfi

Landuzzi

Nicoletti

et al. 2005

The American Journal of Pathology

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We previously showed that a vaccine combining interleukin 12 and allogeneic p185 neu Immunological prevention of tumors is a feasible possibility especially in light of both the encouraging results obtained in preclinical models of neoplasia and of the recent advances in detection of healthy individuals at high risk of developing cancer. 1,2 Transgenic mice expressing the HER-2/neu oncogene under tissue-specific transcriptional control of the mouse mammary tumor virus promoter (MMTV-LTR) represent a suitable model of mammary carcinogenesis. HER-2/neu is overexpressed in 25 to 30% of human breast cancers, influencing biological features and prognosis of the tumor, and the natural history of HER-2/neu transgenic mammary tumors closely resembles that of human breast carcinoma, from atypical hyperplasia to carcinoma in situ and invasive tumor. 3 Among HER-2/neu transgenic mice, BALB-NeuT mice harboring a mutated version of the rat neu oncogene represent a very aggressive model of mammary carcinogenesis because they develop multifocal mamSupported by the

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confidence: 99%

Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma

Astolfi

Landuzzi

Nicoletti

et al. 2005

The American Journal of Pathology

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“…2 In these mice mammary carcinoma can be almost completely prevented by the life-long vaccination with an engineered IL12-producing allogeneic HER2/neu-positive cell vaccine through mechanisms that include host production of anti-neu antibodies and IFNγ. 3 , 5 , 6 In search of more efficient vaccine schedules, we investigated the efficacy of combining vaccination with a monoclonal antibody triggering OX40 (aOX40). A suboptimal vaccine schedule was chosen to observe either increased or decreased preventive efficacy: mice were therefore vaccinated starting at 10 weeks of age for three monthly cycles.…”

Section: Resultsmentioning

confidence: 99%

“…3 Each vaccine dose consisted of 2 × 10 6 cells, proliferation-blocked by treatment with mitomycin C (40 μg/ml Sigma-Aldrich, Milan, Italy), administered intraperitoneally in 0.4 ml of phosphate-buffered saline (PBS) (Invitrogen, Milan, Italy). Control mice received PBS alone.…”

Section: Methodsmentioning

confidence: 99%

“…To determine the level of anti-vaccine antibodies, sera diluted 1:65 were used in indirect immunofluorescence assay to stain viable TT12.E2 cells (HER2/neu overexpressing and H-2 q positive) followed by cytofluorometric analysis as previously described. 3 The intensity of fluorescence of each serum sample was normalized to the expression of rat HER2/neu by the target cells (determined using the monoclonal antibody Ab4, clone 7.16.4, 5 μg/ml, Oncogene Research Products, Cambridge, MA, USA). Anti-H-2 q antibodies were determined by indirect immunofluorescence assay against N202.1E cells (HER2/neu-negative and H-2 q positive).…”

Section: Methodsmentioning

confidence: 99%

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OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis

et al. 2018

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This study evaluated the effects of combining an OX40 agonistic antibody (aOX40) with a cell vaccine targeting HER2/neu, called “Triplex”. Such HER2/neu cell vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic histocompatibility antigens) and was previously found able to prevent autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40 administration, concomitantly or after cell vaccination, gave opposite results. Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu antibodies and to a higher level of Treg activation. On the contrary, aOX40 administration after the completion of vaccination slightly but significantly increased immunopreventive vaccine efficacy, and led to increased production of GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the schedule of aOX40 administration.

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“…53 The immune protection elicited was independent of CTL activity and the IL-12-engineered cell vaccine elicited a high production of IFN-gamma and IL-4 and a strong anti-HER-2/neu antibody response. Immune protection was lost or markedly impaired in BALB-neuT mice lacking IFN-gamma or antibody production, respectively.…”

Section: Transgenic Tumor Models and Candidate Vaccinesmentioning

confidence: 95%

The rationale for prophylactic cancer vaccines and need for a paradigm shift

Sobol

2006

Cancer Gene Ther

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Immunoprevention of HER-2/ neu Transgenic Mammary Carcinoma through an Interleukin 12-Engineered Allogeneic Cell Vaccine

Abstract: ABSTRACT

Cited by 78 publications

References 43 publications

Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma

Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma

OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis

The rationale for prophylactic cancer vaccines and need for a paradigm shift

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