title: DNA vaccination against rat her-2/Neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice.
abstract: The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185(+) transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA vaccination elicits anti-r-p185 Ab, but only a marginal CTL reactivity, and protects against a TUBO cell challenge. Massive reactive infiltration is associated with TUBO cell rejection. In BALB/c mice transgenic for the rat Her-2/neu gene (BALB-neuT), DNA vaccination elicits a lower anti-r-p185 Ab response, no CTL activity and only incompletely protects against TUBO cells, but markedly hampers the progression of carcinogenesis. At 33 wk of age, when control BALB-neuT mice display palpable tumors in all mammary glands, about 60% of immunized mice are tumor free, and tumor multiplicity is markedly reduced. Tumor-free mammary glands still display the atypical hyperplasia of the early stages of carcinogenesis, and a marked down-modulation of r-p185, along with a massive reactive infiltrate. However, BALB-neuT mice protected against mammary carcinogenesis fail to efficiently reject a TUBO cell challenge. This suggests that the mechanisms required for the rejection of transplantable tumors may not coincide with those that inhibit the slow progression of carcinogenesis.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rovero
authors.forename: A
authors.initials: A
authors.lastname: Amici
authors.forename: E
authors.initials: E
authors.lastname: Di Carlo
authors.forename: R
authors.initials: R
authors.lastname: Bei
authors.forename: P
authors.initials: P
authors.lastname: Nanni
authors.forename: E
authors.initials: E
authors.lastname: Quaglino
authors.forename: P
authors.initials: P
authors.lastname: Porcedda
authors.forename: K
authors.initials: K
authors.lastname: Boggio
authors.forename: A
authors.initials: A
authors.lastname: Smorlesi
authors.forename: P L
authors.initials: PL
authors.lastname: Lollini
authors.forename: L
authors.initials: L
authors.lastname: Landuzzi
authors.forename: M P
authors.initials: MP
authors.lastname: Colombo
authors.forename: M
authors.initials: M
authors.lastname: Giovarelli
authors.forename: P
authors.initials: P
authors.lastname: Musiani
authors.forename: G
authors.initials: G
authors.lastname: Forni
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D018275:Carcinoma, Lobular / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation / Q000276:immunology* / Q000473:pathology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000637:transplantation; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D019444:Vaccines, DNA