DNA vaccination against rat her-2/Neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice.
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.
Rovero
S
S
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Amici
A
A
Di Carlo
E
E
Bei
R
R
Nanni
P
P
Quaglino
E
E
Porcedda
P
P
Boggio
K
K
Smorlesi
A
A
Lollini
P L
PL
Landuzzi
L
L
Colombo
M P
MP
Giovarelli
M
M
Musiani
P
P
Forni
G
G
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*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D019444:Vaccines, DNA