CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge

L. Elia, L. Aurisicchio, A. Facciabene, P. Giannetti, G. Ciliberto, N. La Monica, F. Palombo

Research output: Contribution to journalArticle

Abstract

Cancer vaccines are a promising approach to treating tumors or preventing tumor relapse through induction of an immune response against tumor-associated antigens (TAA). One major obstacle to successful therapy is the immunological tolerance against self-antigens which limits an effective antitumor immune response. As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4+CD25+ regulatory T cells. This vaccination modality resulted in increased CEA-specific CD8 +, CD4+ T cells and antibody response. The appearance of a CD4+ T-cell response correlated with a stronger memory response. The combined CD25+ inactivation and genetic vaccination resulted in significant tumor protection in a metastatic tumor model. Non-invasive tumor visualization showed that not only primary tumors were reduced, but also hepatic metastases. Our results support the viability of this cancer vaccine strategy as an adjuvant treatment to prevent tumor relapse in cancer patients.

Original languageEnglish
Pages (from-to)201-210
Number of pages10
JournalCancer Gene Therapy
Volume14
Issue number2
DOIs
Publication statusPublished - Feb 2007

Fingerprint

Adenovirus Vaccines
Regulatory T-Lymphocytes
T-Lymphocytes
Neoplasms
Cancer Vaccines
Vaccination
Autoantigens
Neoplasm Antigens
Recurrence
Adenoviridae
Antibody Formation
Vaccines
Animal Models
Neoplasm Metastasis

Keywords

  • Adeno FOXP3
  • CD25
  • CD8+
  • CEA
  • Tumor

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge. / Elia, L.; Aurisicchio, L.; Facciabene, A.; Giannetti, P.; Ciliberto, G.; La Monica, N.; Palombo, F.

In: Cancer Gene Therapy, Vol. 14, No. 2, 02.2007, p. 201-210.

Research output: Contribution to journalArticle

Elia, L. ; Aurisicchio, L. ; Facciabene, A. ; Giannetti, P. ; Ciliberto, G. ; La Monica, N. ; Palombo, F. / CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge. In: Cancer Gene Therapy. 2007 ; Vol. 14, No. 2. pp. 201-210.
@article{b7858880586248eaa8295573c3ffc2fe,
title = "CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge",
abstract = "Cancer vaccines are a promising approach to treating tumors or preventing tumor relapse through induction of an immune response against tumor-associated antigens (TAA). One major obstacle to successful therapy is the immunological tolerance against self-antigens which limits an effective antitumor immune response. As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4+CD25+ regulatory T cells. This vaccination modality resulted in increased CEA-specific CD8 +, CD4+ T cells and antibody response. The appearance of a CD4+ T-cell response correlated with a stronger memory response. The combined CD25+ inactivation and genetic vaccination resulted in significant tumor protection in a metastatic tumor model. Non-invasive tumor visualization showed that not only primary tumors were reduced, but also hepatic metastases. Our results support the viability of this cancer vaccine strategy as an adjuvant treatment to prevent tumor relapse in cancer patients.",
keywords = "Adeno FOXP3, CD25, CD8+, CEA, Tumor",
author = "L. Elia and L. Aurisicchio and A. Facciabene and P. Giannetti and G. Ciliberto and {La Monica}, N. and F. Palombo",
year = "2007",
month = "2",
doi = "10.1038/sj.cgt.7701004",
language = "English",
volume = "14",
pages = "201--210",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge

AU - Elia, L.

AU - Aurisicchio, L.

AU - Facciabene, A.

AU - Giannetti, P.

AU - Ciliberto, G.

AU - La Monica, N.

AU - Palombo, F.

PY - 2007/2

Y1 - 2007/2

N2 - Cancer vaccines are a promising approach to treating tumors or preventing tumor relapse through induction of an immune response against tumor-associated antigens (TAA). One major obstacle to successful therapy is the immunological tolerance against self-antigens which limits an effective antitumor immune response. As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4+CD25+ regulatory T cells. This vaccination modality resulted in increased CEA-specific CD8 +, CD4+ T cells and antibody response. The appearance of a CD4+ T-cell response correlated with a stronger memory response. The combined CD25+ inactivation and genetic vaccination resulted in significant tumor protection in a metastatic tumor model. Non-invasive tumor visualization showed that not only primary tumors were reduced, but also hepatic metastases. Our results support the viability of this cancer vaccine strategy as an adjuvant treatment to prevent tumor relapse in cancer patients.

AB - Cancer vaccines are a promising approach to treating tumors or preventing tumor relapse through induction of an immune response against tumor-associated antigens (TAA). One major obstacle to successful therapy is the immunological tolerance against self-antigens which limits an effective antitumor immune response. As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4+CD25+ regulatory T cells. This vaccination modality resulted in increased CEA-specific CD8 +, CD4+ T cells and antibody response. The appearance of a CD4+ T-cell response correlated with a stronger memory response. The combined CD25+ inactivation and genetic vaccination resulted in significant tumor protection in a metastatic tumor model. Non-invasive tumor visualization showed that not only primary tumors were reduced, but also hepatic metastases. Our results support the viability of this cancer vaccine strategy as an adjuvant treatment to prevent tumor relapse in cancer patients.

KW - Adeno FOXP3

KW - CD25

KW - CD8+

KW - CEA

KW - Tumor

UR - http://www.scopus.com/inward/record.url?scp=33846212289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846212289&partnerID=8YFLogxK

U2 - 10.1038/sj.cgt.7701004

DO - 10.1038/sj.cgt.7701004

M3 - Article

C2 - 17053815

AN - SCOPUS:33846212289

VL - 14

SP - 201

EP - 210

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 2

ER -