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Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions
Elena Quaglino, … , Raffaele Calogero, Federica Cavallo
Elena Quaglino, … , Raffaele Calogero, Federica Cavallo
Published March 1, 2004
Citation Information: J Clin Invest. 2004;113(5):709-717. https://doi.org/10.1172/JCI19850.
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Categories: Article Immunology

Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions

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Abstract

While much experimental data shows that vaccination efficiently inhibits a subsequent challenge by a transplantable tumor, its ability to inhibit the progress of autochthonous preneoplastic lesions is virtually unknown. In this article, we show that a combined DNA and cell vaccine persistently inhibits such lesions in a murine HER-2/neu mammary carcinogenesis model. At 10 weeks of age, all of the ten mammary gland samples from HER-2/neu–transgenic mice displayed foci of hyperplasia that progressed to invasive tumors. Vaccination with plasmids coding for the transmembrane and extracellular domain of rat p185neu followed by a boost with rp185neu+ allogeneic cells secreting IFN-γ kept 48% of mice tumor free. At 22 weeks, their mammary glands were indistinguishable from those of 10-week-old untreated mice. Furthermore, the transcription patterns of the two sets of glands coincided. Of the 12,000 genes analyzed, 17 were differentially expressed and related to the antibody response. The use of B cell knockout mice as well as the concordance of morphologic and gene expression data demonstrated that the Ab response is the main mechanism facilitating tumor growth arrest. This finding suggests that a new way can be found to secure the immunologic control of the progression of HER-2/neu preneoplastic lesions.

Authors

Elena Quaglino, Simona Rolla, Manuela Iezzi, Michela Spadaro, Piero Musiani, Carla De Giovanni, Pier Luigi Lollini, Stefania Lanzardo, Guido Forni, Remo Sanges, Stefania Crispi, Pasquale De Luca, Raffaele Calogero, Federica Cavallo

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Figure 1

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Effects of TM-ECD vaccination and p185neu/alloq-IFNγ cells boost on the ...
Effects of TM-ECD vaccination and p185neu/alloq-IFNγ cells boost on the progression of precancerous lesions in BALB-neuT mice. (A–C) Whole-mount analysis of mammary glands. The nipple areas are indicated by the arrows. Magnification, ×6.3. (A) Wk10nt mammary glands show several atypical hyperplasia foci forming multiple ductal side buds, sometimes coalescing in larger nodules representing in situ carcinomas. (B) Wk22nt mammary glands; a large portion is occupied by nodular masses corresponding to invasive carcinomas. (C) Wk22pb mammary glands. (D) Percentage of tumor-free mice and (E) tumor multiplicity in BALB-neuT mice. TM-ECD–vaccinated mice (open squares, 18 mice); p185neu/alloq-IFNγ cell–vaccinated mice (open circles, 5 mice); primed-and-boosted mice (filled squares, 21 mice); and primed-and-boosted BALB-neuT/μKO mice (filled triangles, 5 mice). Tumor-free survival curve of primed-and-boosted BALB-neuT mice is significantly different (Mantel-Haenszel test) from that of TM-ECD–vaccinated BALB-neuT mice (P < 0.0001) and that of primed-and-boosted BALB-neuT/μKO mice (P < 0.009). From week 23, the mean tumor multiplicity in primed-and-boosted BALB-neuT mice is significantly different from that of TM-ECD–vaccinated mice (P = 0.0002, Student’s t test). Vertical bars represent SE. This experiment was repeated three times. The cumulative data are shown.
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