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Immunological Prevention of Spontaneous Mammary Carcinoma in Transgenic Mice

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Final rept. 1 Jul 1998-1 Jul 2001

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Our program was to evaluate the ability of non specific and specific immunity to hamper the carcinogenesis. The ultimate goal was to determine whether this type of approach can be rationally applied in humans at risk. The model used consisted in virgin female mice transgenic for the activated BALB-neuT or amplified FVB-neuN rat Her-2neu oncogene. BALB-neuT mice progress rapidly to multiple mammary carcinomas, while in FVB-neuN carcinogenesis is slow. A timely administration of low doses of IL-l2 elicits in a complex immunological reaction that markedly delay the progression of carcinogenesis and alter the angiogeneic capacity of carcinomas. This prevention by delaying takes place in the absence of any antigenic definition. A much more effective and persistent prevention can be induced by specific immunization against the Her-2neu membrane product p185neu. A strong protection was afforded by vaccination with DNA plasmids coding for p185neu, while no protection was elicited by vaccination with distinct p185neu peptides. p185neu positive allogeneic cells are effective vaccines and their immunogenicity is further increased when these cells are engineered to release IFN-y. All mice vaccinated with allogenic p185neu cells and receiving systemic IL-l2 are tumor free at one year of age. The combination of nonspecific and specific immunostimulation appears to be an effective way to protect the host form an ongoing carcinogenic process.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Pharmacology

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