Genetic immunization against neu?/erbB2 transgenic breast cancer |
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Authors: | Augusto Amici Franco Maria Venanzi Antonio Concetti |
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Institution: | (1) Unit of Genetic Immunization, Department of Biology M.C.A., via F. Camerini, I-62032 Camerino (MC), Italy e-mail: concetti@cambio.unicam.it; venanzi@cambio.unicam.it; augusto@cambio.unicam.it Tel.: +39-737-403258/09 Fax: +39-737-636216, IT |
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Abstract: | erbB2/neu, an overexpressed oncogene product, has been proposed as a human cancer vaccine target. In the present study, transgenic
(rat neuNT oncogene) FVB/neu mice, developing metastasizable mammary carcinoma, were immunized with a plasmid DNA encoding are not
tolerant to the self antigen and sequences. We report that transgenic tumour-bearing mice, like some breast cancer patients
erbB2+X, develop anti-neu autoimmune responses, which can be boosted and skewed to a Th1 phenotype by DNA immunization. Intramuscular
injections of neuNT plasmid drastically reduced (or even prevented in a small number of treated mice) the outgrowth of mammary
neoplasms as well as their metastatic penetrance. Furthermore, DNA immunization caused haemorrhagic necrosis of established
cancer nests, leaving a greatly reduced portion of the tumour burden for the host to cope with. The antitumour activities
we obtained, in this very challenging model for cancer immunotherapy, lay the foundation for DNA-based immunization to control
erbB2/neu-overexpressing neoplasms.
Received: 19 April 1998 / Accepted: 20 August 1998 |
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Keywords: | DNA immunization neu/erbB2 oncogene Transgenic mice Breast cancer Th1 autoimmunity |
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