Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides

Jonathan Baines, Esteban Celis

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

T-cell based immunotherapy is an attractive approach for the treatment of multiple tumor types including cervical carcinoma. Immunostimulating DNA containing unmethylated cytosine-guanine (CpG) motifs have been successfully used as adjuvants to enhance immune responses to vaccines designed to trigger antitumor T-cell responses. Using a murine model of cervical carcinoma, we report here that repeated administration of synthetic oligodeoxynucleotides bearing CpG motifs (CpG-ODNs) without the need of vaccination into animals bearing large, established tumors resulted in significant antitumor effects. Both tumor regressions and extended survival resulting from CpG-ODN therapy required the participation of CD8+ T cells. On the other hand, CD4+ T cells were not only not required, but also appeared to inhibit the therapeutic effect of CpG-ODN. Tumor regression correlated with increased infiltration of CD8+ T cells into the tumors and with enhanced expression of MHC class I and III antigens by the tumor cells. Together, these results indicate that CpG therapy could be promising as a single agent for the treatment of some tumors such as cervical carcinoma.

Original languageEnglish (US)
Pages (from-to)2693-2700
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number7
StatePublished - Jul 1 2003

Fingerprint

Oligodeoxyribonucleotides
T-Lymphocytes
Neoplasms
Carcinoma
Histocompatibility Antigens Class I
Cytosine
Guanine
Therapeutic Uses
Therapeutics
Immunotherapy
Vaccination
Vaccines
DNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. / Baines, Jonathan; Celis, Esteban.

In: Clinical Cancer Research, Vol. 9, No. 7, 01.07.2003, p. 2693-2700.

Research output: Contribution to journalArticle

@article{31d85b5572fd4fa384a049f51a53d69e,
title = "Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides",
abstract = "T-cell based immunotherapy is an attractive approach for the treatment of multiple tumor types including cervical carcinoma. Immunostimulating DNA containing unmethylated cytosine-guanine (CpG) motifs have been successfully used as adjuvants to enhance immune responses to vaccines designed to trigger antitumor T-cell responses. Using a murine model of cervical carcinoma, we report here that repeated administration of synthetic oligodeoxynucleotides bearing CpG motifs (CpG-ODNs) without the need of vaccination into animals bearing large, established tumors resulted in significant antitumor effects. Both tumor regressions and extended survival resulting from CpG-ODN therapy required the participation of CD8+ T cells. On the other hand, CD4+ T cells were not only not required, but also appeared to inhibit the therapeutic effect of CpG-ODN. Tumor regression correlated with increased infiltration of CD8+ T cells into the tumors and with enhanced expression of MHC class I and III antigens by the tumor cells. Together, these results indicate that CpG therapy could be promising as a single agent for the treatment of some tumors such as cervical carcinoma.",
author = "Jonathan Baines and Esteban Celis",
year = "2003",
month = "7",
day = "1",
language = "English (US)",
volume = "9",
pages = "2693--2700",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides

AU - Baines, Jonathan

AU - Celis, Esteban

PY - 2003/7/1

Y1 - 2003/7/1

N2 - T-cell based immunotherapy is an attractive approach for the treatment of multiple tumor types including cervical carcinoma. Immunostimulating DNA containing unmethylated cytosine-guanine (CpG) motifs have been successfully used as adjuvants to enhance immune responses to vaccines designed to trigger antitumor T-cell responses. Using a murine model of cervical carcinoma, we report here that repeated administration of synthetic oligodeoxynucleotides bearing CpG motifs (CpG-ODNs) without the need of vaccination into animals bearing large, established tumors resulted in significant antitumor effects. Both tumor regressions and extended survival resulting from CpG-ODN therapy required the participation of CD8+ T cells. On the other hand, CD4+ T cells were not only not required, but also appeared to inhibit the therapeutic effect of CpG-ODN. Tumor regression correlated with increased infiltration of CD8+ T cells into the tumors and with enhanced expression of MHC class I and III antigens by the tumor cells. Together, these results indicate that CpG therapy could be promising as a single agent for the treatment of some tumors such as cervical carcinoma.

AB - T-cell based immunotherapy is an attractive approach for the treatment of multiple tumor types including cervical carcinoma. Immunostimulating DNA containing unmethylated cytosine-guanine (CpG) motifs have been successfully used as adjuvants to enhance immune responses to vaccines designed to trigger antitumor T-cell responses. Using a murine model of cervical carcinoma, we report here that repeated administration of synthetic oligodeoxynucleotides bearing CpG motifs (CpG-ODNs) without the need of vaccination into animals bearing large, established tumors resulted in significant antitumor effects. Both tumor regressions and extended survival resulting from CpG-ODN therapy required the participation of CD8+ T cells. On the other hand, CD4+ T cells were not only not required, but also appeared to inhibit the therapeutic effect of CpG-ODN. Tumor regression correlated with increased infiltration of CD8+ T cells into the tumors and with enhanced expression of MHC class I and III antigens by the tumor cells. Together, these results indicate that CpG therapy could be promising as a single agent for the treatment of some tumors such as cervical carcinoma.

UR - http://www.scopus.com/inward/record.url?scp=0037479773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037479773&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 2693

EP - 2700

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 7

ER -