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Low effectiveness of DNA vaccination against HER-2/neu in ageing
Mauro Provinciali1, Arianna Smorlesi, Alessia Donnini
1Laboratory of Tumor Immunology, INRCA Gerontology Research Department, Immunology Centre, Via Birarelli 8, 60121 Ancona, Italy. m.provinciali@inrca.it
Abstract:
We evaluated the effectiveness of vaccination with a HER-2/neu DNA plasmid to induce protective immunity against HER-2/neu overexpressing syngeneic TUBO tumour cells in old ages. Young and old Balb/c mice received three immunizations with a pCMVneuNT DNA plasmid and, successively, were challenged with TUBO cells. Young mice were completely protected whereas less than 60% protection was observed in old mice. Anti-p185(neu) antibodies were found in the sera from both young and old immunized mice, even if antibody production was significantly higher in young in comparison with old mice. Similarly, higher anti-p185(neu) lymphocyte proliferation was induced in young than in old mice. No anti-p185(neu) cytotoxicity was found in lymphocytes from old animals. We conclude that anticancer DNA vaccination has a lower effectiveness in old than in young ages.
Insights
Anticancer DNA vaccination using a HER-2/neu DNA plasmid showed reduced effectiveness in older mice compared to younger mice. This age-related decline in immune response impacts protective immunity against HER-2/neu tumors.
Area of Science:
- Immunology
- Oncology
- Gerontology
Background:
- HER-2/neu overexpression is common in certain cancers.
- DNA vaccines offer a promising approach for cancer immunotherapy.
- Age can significantly influence immune responses and vaccine efficacy.
Purpose of the Study:
- To evaluate the effectiveness of HER-2/neu DNA plasmid vaccination in inducing protective immunity in aged mice.
- To compare the immune response to DNA vaccination in young versus old mice against HER-2/neu overexpressing tumors.
Main Methods:
- Balb/c mice (young and old) were immunized with a pCMVneuNT DNA plasmid.
- Mice were subsequently challenged with syngeneic TUBO tumor cells.
- Humoral (antibody production) and cellular (lymphocyte proliferation and cytotoxicity) immune responses were assessed.
Main Results:
- Young mice showed complete protection against TUBO cells, while old mice exhibited less than 60% protection.
- Both age groups produced anti-p185(neu) antibodies, but levels were significantly higher in young mice.
- Lymphocyte proliferation was higher in young mice; no anti-p185(neu) cytotoxicity was detected in old mice.
Conclusions:
- Anticancer DNA vaccination against HER-2/neu is less effective in aged individuals compared to younger ones.
- Age-related decline in both antibody production and cellular immunity contributes to reduced vaccine efficacy.
- These findings highlight the importance of age as a factor in the effectiveness of cancer DNA vaccines.