Abstract
Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and humans. As these Ags are preferentially expressed by neoplastic tissues, they might represent an ideal target for active immunization by genetic vaccination. However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two products of the env gene of an endogenous murine leukemia virus, elicited a weak Ag-specific T lymphocyte response and resulted in partial protection from challenge with mouse tumors possessing these Ags. Depletion experiments showed that CD8+, but not CD4+, T lymphocytes were crucial for the antitumor activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb increased the therapeutic potential of genetic vaccination, but only when given during the tumor rejection phase and not at the time of immunization. This effect correlated with a dramatic increase in the number of ERV-specific CD8+ T lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8 + T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.
| Original language | English |
|---|---|
| Pages (from-to) | 6396-6405 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 171 |
| Issue number | 12 |
| State | Published - Dec 15 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Effective Genetic Vaccination with a Widely Shared Endogenous Retroviral Tumor Antigen Requires CD40 Stimulation during Tumor Rejection Phase. / Bronte, Vincenzo; Cingarlini, Sara; Apolloni, Elisa; Serafini, Paolo; Marigo, Ilaria; De Santo, Carmela; Macino, Beatrice; Marin, Oriano; Zanovello, Paola.
In: Journal of Immunology, Vol. 171, No. 12, 15.12.2003, p. 6396-6405.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effective Genetic Vaccination with a Widely Shared Endogenous Retroviral Tumor Antigen Requires CD40 Stimulation during Tumor Rejection Phase
AU - Bronte, Vincenzo
AU - Cingarlini, Sara
AU - Apolloni, Elisa
AU - Serafini, Paolo
AU - Marigo, Ilaria
AU - De Santo, Carmela
AU - Macino, Beatrice
AU - Marin, Oriano
AU - Zanovello, Paola
PY - 2003/12/15
Y1 - 2003/12/15
N2 - Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and humans. As these Ags are preferentially expressed by neoplastic tissues, they might represent an ideal target for active immunization by genetic vaccination. However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two products of the env gene of an endogenous murine leukemia virus, elicited a weak Ag-specific T lymphocyte response and resulted in partial protection from challenge with mouse tumors possessing these Ags. Depletion experiments showed that CD8+, but not CD4+, T lymphocytes were crucial for the antitumor activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb increased the therapeutic potential of genetic vaccination, but only when given during the tumor rejection phase and not at the time of immunization. This effect correlated with a dramatic increase in the number of ERV-specific CD8+ T lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8 + T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.
AB - Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and humans. As these Ags are preferentially expressed by neoplastic tissues, they might represent an ideal target for active immunization by genetic vaccination. However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two products of the env gene of an endogenous murine leukemia virus, elicited a weak Ag-specific T lymphocyte response and resulted in partial protection from challenge with mouse tumors possessing these Ags. Depletion experiments showed that CD8+, but not CD4+, T lymphocytes were crucial for the antitumor activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb increased the therapeutic potential of genetic vaccination, but only when given during the tumor rejection phase and not at the time of immunization. This effect correlated with a dramatic increase in the number of ERV-specific CD8+ T lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8 + T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.
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M3 - Article
VL - 171
SP - 6396
EP - 6405
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -