Abstract
Abnormal tumor vasculature impairs T lymphocyte adhesion to endothelial cells and lymphocyte extravasation into neoplastictissues, limiting the therapeutic potential of both active and adoptive immunotherapies. We have found that treatment of tumor-bearing mice with NGR-TNF, a Cys-Asn-Gly-Arg-Cys peptide-TNF fusion product capable of altering the endothelial barrier function and improving drug penetration in tumors, associated with the intratumor upregulation of leukocyte-endothelial cell adhesion molecules, the release of proinflammatory cytokines and chemokines, and the infiltration of tumor-specific effector CD8 + T cells. As a result, NGR-TNF enhanced the therapeutic activity of adoptive and active immunotherapy, delaying tumor growth and prolonging survival. Furthermore, we have found that therapeutic effects of these combinations can be further increased by the addition of chemotherapy. Thus, these findings might be relevant for the design of novel immunotherapeutic approaches for cancer patients.
| Original language | English |
|---|---|
| Pages (from-to) | 2687-2694 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 188 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2012 |
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ASJC Scopus subject areas
- Immunology
Cite this
Targeting TNF-α to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy. / Calcinotto, Arianna; Grioni, Matteo; Jachetti, Elena; Curnis, Flavio; Mondino, Anna; Parmiani, Giorgio; Corti, Angelo; Bellone, Matteo.
In: Journal of Immunology, Vol. 188, No. 6, 15.03.2012, p. 2687-2694.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting TNF-α to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy
AU - Calcinotto, Arianna
AU - Grioni, Matteo
AU - Jachetti, Elena
AU - Curnis, Flavio
AU - Mondino, Anna
AU - Parmiani, Giorgio
AU - Corti, Angelo
AU - Bellone, Matteo
PY - 2012/3/15
Y1 - 2012/3/15
N2 - Abnormal tumor vasculature impairs T lymphocyte adhesion to endothelial cells and lymphocyte extravasation into neoplastictissues, limiting the therapeutic potential of both active and adoptive immunotherapies. We have found that treatment of tumor-bearing mice with NGR-TNF, a Cys-Asn-Gly-Arg-Cys peptide-TNF fusion product capable of altering the endothelial barrier function and improving drug penetration in tumors, associated with the intratumor upregulation of leukocyte-endothelial cell adhesion molecules, the release of proinflammatory cytokines and chemokines, and the infiltration of tumor-specific effector CD8 + T cells. As a result, NGR-TNF enhanced the therapeutic activity of adoptive and active immunotherapy, delaying tumor growth and prolonging survival. Furthermore, we have found that therapeutic effects of these combinations can be further increased by the addition of chemotherapy. Thus, these findings might be relevant for the design of novel immunotherapeutic approaches for cancer patients.
AB - Abnormal tumor vasculature impairs T lymphocyte adhesion to endothelial cells and lymphocyte extravasation into neoplastictissues, limiting the therapeutic potential of both active and adoptive immunotherapies. We have found that treatment of tumor-bearing mice with NGR-TNF, a Cys-Asn-Gly-Arg-Cys peptide-TNF fusion product capable of altering the endothelial barrier function and improving drug penetration in tumors, associated with the intratumor upregulation of leukocyte-endothelial cell adhesion molecules, the release of proinflammatory cytokines and chemokines, and the infiltration of tumor-specific effector CD8 + T cells. As a result, NGR-TNF enhanced the therapeutic activity of adoptive and active immunotherapy, delaying tumor growth and prolonging survival. Furthermore, we have found that therapeutic effects of these combinations can be further increased by the addition of chemotherapy. Thus, these findings might be relevant for the design of novel immunotherapeutic approaches for cancer patients.
UR - http://www.scopus.com/inward/record.url?scp=84857829255&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857829255&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1101877
DO - 10.4049/jimmunol.1101877
M3 - Article
C2 - 22323546
AN - SCOPUS:84857829255
VL - 188
SP - 2687
EP - 2694
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -