Accession Number : ADA398103


Title :   Immunological Prevention of Spontaneous Mammary Carcinoma in Transgenic Mice


Descriptive Note : Final rept. 1 Jul 1998-1 Jul 2001


Corporate Author : TURIN UNIV (ITALY)


Personal Author(s) : Forni, Guido


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a398103.pdf


Report Date : Aug 2001


Pagination or Media Count : 139


Abstract : 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-2/neu 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-2/neu 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.


Descriptors :   *IMMUNITY , *BREAST CANCER , PEPTIDES , NEOPLASMS , DEOXYRIBONUCLEIC ACIDS , GENES , IMMUNOLOGY , CARCINOGENS , T LYMPHOCYTES , INHIBITION , CELLS(BIOLOGY) , FEMALES , VACCINES , MAMMARY GLANDS , INJECTIONS(MEDICINE) , GROWTH(PHYSIOLOGY) , TRANSCRIPTION(GENETICS) , ONCOGENESIS


Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE