Abstract
Main obstacles to cancer vaccine efficacy are pre-existing antigenic load and immunoescape mechanisms, including tolerance against self tumor-associated antigens. Here we explored the role of tolerance in an antimetastatic vaccine approach based on dendritic cell-tumor cell (DC-TC) hybrids, thanks to the comparison between BALB-neuT mice, transgenic for and tolerant to rat HER-2/neu, with their nontolerant strain of origin BALB/c. Allogeneic DC-TC hybrid vaccine displayed a high antimetastatic activity in non-tolerant mice, but was far less effective in tolerant mice, even with intensified vaccine schedule. Tolerant BALB-neuT mice revealed a reduced ability to mount polarized Th1 responses. A further attempt to increase the antimetastatic activity by using LPS-matured DC hybrids failed. Allogeneic LPS-matured DC-TC hybrids induced high IFN-γ levels, but concomitantly also the highest production of IL-4 and IL-10 suggesting activation of mechanisms sustaining regulatory cells able to blunt vaccine efficacy. Our data in tolerant versus non-tolerant hosts suggest that clinical translation of effective DC-based strategies could benefit from more extensive investigations in tolerant transgenic models.
| Original language | English |
|---|---|
| Pages (from-to) | 4690-4697 |
| Number of pages | 8 |
| Journal | Vaccine |
| Volume | 29 |
| Issue number | 29-30 |
| DOIs | |
| Publication status | Published - Jun 24 2011 |
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Keywords
- Cancer vaccines
- Dendritic cells
- HER-2/neu
- Metastasis
- Transgenic mice
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
- Molecular Medicine
Cite this
HER-2/neu tolerant and non-tolerant mice for fine assessment of antimetastatic potency of dendritic cell-tumor cell hybrid vaccines. / Landuzzi, Lorena; Antognoli, Agnese; Nicoletti, Giordano; Croci, Stefania; Palladini, Arianna; Ianzano, Marianna Lucia; Murgo, Annalisa; Stivani, Valeria; Grosso, Valentina; Nanni, Patrizia; De Giovanni, Carla; Lollini, Pier Luigi.
In: Vaccine, Vol. 29, No. 29-30, 24.06.2011, p. 4690-4697.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HER-2/neu tolerant and non-tolerant mice for fine assessment of antimetastatic potency of dendritic cell-tumor cell hybrid vaccines
AU - Landuzzi, Lorena
AU - Antognoli, Agnese
AU - Nicoletti, Giordano
AU - Croci, Stefania
AU - Palladini, Arianna
AU - Ianzano, Marianna Lucia
AU - Murgo, Annalisa
AU - Stivani, Valeria
AU - Grosso, Valentina
AU - Nanni, Patrizia
AU - De Giovanni, Carla
AU - Lollini, Pier Luigi
PY - 2011/6/24
Y1 - 2011/6/24
N2 - Main obstacles to cancer vaccine efficacy are pre-existing antigenic load and immunoescape mechanisms, including tolerance against self tumor-associated antigens. Here we explored the role of tolerance in an antimetastatic vaccine approach based on dendritic cell-tumor cell (DC-TC) hybrids, thanks to the comparison between BALB-neuT mice, transgenic for and tolerant to rat HER-2/neu, with their nontolerant strain of origin BALB/c. Allogeneic DC-TC hybrid vaccine displayed a high antimetastatic activity in non-tolerant mice, but was far less effective in tolerant mice, even with intensified vaccine schedule. Tolerant BALB-neuT mice revealed a reduced ability to mount polarized Th1 responses. A further attempt to increase the antimetastatic activity by using LPS-matured DC hybrids failed. Allogeneic LPS-matured DC-TC hybrids induced high IFN-γ levels, but concomitantly also the highest production of IL-4 and IL-10 suggesting activation of mechanisms sustaining regulatory cells able to blunt vaccine efficacy. Our data in tolerant versus non-tolerant hosts suggest that clinical translation of effective DC-based strategies could benefit from more extensive investigations in tolerant transgenic models.
AB - Main obstacles to cancer vaccine efficacy are pre-existing antigenic load and immunoescape mechanisms, including tolerance against self tumor-associated antigens. Here we explored the role of tolerance in an antimetastatic vaccine approach based on dendritic cell-tumor cell (DC-TC) hybrids, thanks to the comparison between BALB-neuT mice, transgenic for and tolerant to rat HER-2/neu, with their nontolerant strain of origin BALB/c. Allogeneic DC-TC hybrid vaccine displayed a high antimetastatic activity in non-tolerant mice, but was far less effective in tolerant mice, even with intensified vaccine schedule. Tolerant BALB-neuT mice revealed a reduced ability to mount polarized Th1 responses. A further attempt to increase the antimetastatic activity by using LPS-matured DC hybrids failed. Allogeneic LPS-matured DC-TC hybrids induced high IFN-γ levels, but concomitantly also the highest production of IL-4 and IL-10 suggesting activation of mechanisms sustaining regulatory cells able to blunt vaccine efficacy. Our data in tolerant versus non-tolerant hosts suggest that clinical translation of effective DC-based strategies could benefit from more extensive investigations in tolerant transgenic models.
KW - Cancer vaccines
KW - Dendritic cells
KW - HER-2/neu
KW - Metastasis
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=79960637991&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960637991&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2011.04.096
DO - 10.1016/j.vaccine.2011.04.096
M3 - Article
C2 - 21569812
AN - SCOPUS:79960637991
VL - 29
SP - 4690
EP - 4697
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 29-30
ER -