Targeting TNF-α to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy

Arianna Calcinotto, Matteo Grioni, Elena Jachetti, Flavio Curnis, Anna Mondino, Giorgio Parmiani, Angelo Corti, Matteo Bellone

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)2687-2694
Number of pages8
JournalJournal of Immunology
Volume188
Issue number6
DOIs
Publication statusPublished - Mar 15 2012

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Immunotherapy
Lymphocytes
Adoptive Immunotherapy
Active Immunotherapy
Neoplasms
Therapeutics
Endothelial Cells
T-Lymphocytes
Cell Adhesion Molecules
Therapeutic Uses
Chemokines
Leukocytes
Up-Regulation
Cytokines
Drug Therapy
Peptides
Survival
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

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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 journalArticle

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AU - Calcinotto, Arianna

AU - Grioni, Matteo

AU - Jachetti, Elena

AU - Curnis, Flavio

AU - Mondino, Anna

AU - Parmiani, Giorgio

AU - Corti, Angelo

AU - Bellone, Matteo

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