Abstract
The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of mammary carcinoma progression in HER-2/neu transgenic mice. The vaccine consisted of transgenic mammary carcinoma cells expressing HER-2/neu and two adjuvants: allogeneic class I histocompatibility antigens and interleukin (IL)-12. Vaccination of mice bearing lung micrometastases resulted in a 90% inhibition of metastasis development, whereas vaccination of mice with incipient local tumors was ineffective. The antimetastatic response was hampered by immune tolerance, as the protection of transgenic mice was lower than that of wild-type congenics not tolerant to HER-2/neu. A significant gain in immunotherapeutic activity in transgenic mice was obtained through the coadministration of anti-CD25 monoclonal antibody targeting regulatory T cells, which resulted in a >99% inhibition of metastasis. The immune responses elicited in transgenic mice comprised the activation of lung granulocytes and macrophages and of systemic adaptive responses based on helper T cells and their cytokines (IFN-γ and IL-4) and anti-HER-2/neu antibodies. Dissection of relevant antimetastatic mechanisms by means of knockout mice and of depleting antibodies revealed a major difference between tumor prevention, which was completely dependent on anti-HER-2/neu antibodies, and metastasis therapy, which was antibody independent. In conclusion, a vaccine successfully developed for cancer immunoprevention showed a strong therapeutic activity against lung metastases mediated by protective immune mechanisms distinct from those preventing the onset of primary mammary carcinoma.
| Original language | English |
|---|---|
| Pages (from-to) | 11037-11044 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - Nov 15 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Antimetastatic activity of a preventive cancer vaccine. / Nanni, Patrizia; Nicoletti, Giordano; Palladini, Arianna; Croci, Stefania; Murgo, Annalisa; Antognoli, Agnese; Landuzzi, Lorena; Fabbi, Marina; Ferrini, Silvano; Musiani, Piero; Iezzi, Manuela; De Giovanni, Carla; Lollini, Pier Luigi.
In: Cancer Research, Vol. 67, No. 22, 15.11.2007, p. 11037-11044.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antimetastatic activity of a preventive cancer vaccine
AU - Nanni, Patrizia
AU - Nicoletti, Giordano
AU - Palladini, Arianna
AU - Croci, Stefania
AU - Murgo, Annalisa
AU - Antognoli, Agnese
AU - Landuzzi, Lorena
AU - Fabbi, Marina
AU - Ferrini, Silvano
AU - Musiani, Piero
AU - Iezzi, Manuela
AU - De Giovanni, Carla
AU - Lollini, Pier Luigi
PY - 2007/11/15
Y1 - 2007/11/15
N2 - The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of mammary carcinoma progression in HER-2/neu transgenic mice. The vaccine consisted of transgenic mammary carcinoma cells expressing HER-2/neu and two adjuvants: allogeneic class I histocompatibility antigens and interleukin (IL)-12. Vaccination of mice bearing lung micrometastases resulted in a 90% inhibition of metastasis development, whereas vaccination of mice with incipient local tumors was ineffective. The antimetastatic response was hampered by immune tolerance, as the protection of transgenic mice was lower than that of wild-type congenics not tolerant to HER-2/neu. A significant gain in immunotherapeutic activity in transgenic mice was obtained through the coadministration of anti-CD25 monoclonal antibody targeting regulatory T cells, which resulted in a >99% inhibition of metastasis. The immune responses elicited in transgenic mice comprised the activation of lung granulocytes and macrophages and of systemic adaptive responses based on helper T cells and their cytokines (IFN-γ and IL-4) and anti-HER-2/neu antibodies. Dissection of relevant antimetastatic mechanisms by means of knockout mice and of depleting antibodies revealed a major difference between tumor prevention, which was completely dependent on anti-HER-2/neu antibodies, and metastasis therapy, which was antibody independent. In conclusion, a vaccine successfully developed for cancer immunoprevention showed a strong therapeutic activity against lung metastases mediated by protective immune mechanisms distinct from those preventing the onset of primary mammary carcinoma.
AB - The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of mammary carcinoma progression in HER-2/neu transgenic mice. The vaccine consisted of transgenic mammary carcinoma cells expressing HER-2/neu and two adjuvants: allogeneic class I histocompatibility antigens and interleukin (IL)-12. Vaccination of mice bearing lung micrometastases resulted in a 90% inhibition of metastasis development, whereas vaccination of mice with incipient local tumors was ineffective. The antimetastatic response was hampered by immune tolerance, as the protection of transgenic mice was lower than that of wild-type congenics not tolerant to HER-2/neu. A significant gain in immunotherapeutic activity in transgenic mice was obtained through the coadministration of anti-CD25 monoclonal antibody targeting regulatory T cells, which resulted in a >99% inhibition of metastasis. The immune responses elicited in transgenic mice comprised the activation of lung granulocytes and macrophages and of systemic adaptive responses based on helper T cells and their cytokines (IFN-γ and IL-4) and anti-HER-2/neu antibodies. Dissection of relevant antimetastatic mechanisms by means of knockout mice and of depleting antibodies revealed a major difference between tumor prevention, which was completely dependent on anti-HER-2/neu antibodies, and metastasis therapy, which was antibody independent. In conclusion, a vaccine successfully developed for cancer immunoprevention showed a strong therapeutic activity against lung metastases mediated by protective immune mechanisms distinct from those preventing the onset of primary mammary carcinoma.
UR - http://www.scopus.com/inward/record.url?scp=36348966738&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36348966738&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-2499
DO - 10.1158/0008-5472.CAN-07-2499
M3 - Article
C2 - 18006850
AN - SCOPUS:36348966738
VL - 67
SP - 11037
EP - 11044
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 22
ER -