The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors

Chie Kudo-Saito, Jeffrey Schlom, Kevin Camphausen, C. Norman Coleman, James W. Hodge

Research output: Contribution to journalArticle

Abstract

Purpose: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. Experimental Design: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+ suppressor cells. Results: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non - self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). Conclusions: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.

Original languageEnglish (US)
Pages (from-to)4533-4544
Number of pages12
JournalClinical Cancer Research
Volume11
Issue number12
DOIs
StatePublished - Jun 15 2005
Externally publishedYes

Fingerprint

Active Immunotherapy
Cancer Vaccines
Radiation
Monoclonal Antibodies
Neoplasms
Combined Vaccines
Histocompatibility Antigens Class II
Autoantigens
Neoplasm Antigens
T-Lymphocytes
Vaccines
Clinical Trials
Therapeutics
Vaccination
Research Design
Up-Regulation
Antigens

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors. / Kudo-Saito, Chie; Schlom, Jeffrey; Camphausen, Kevin; Coleman, C. Norman; Hodge, James W.

In: Clinical Cancer Research, Vol. 11, No. 12, 15.06.2005, p. 4533-4544.

Research output: Contribution to journalArticle

Kudo-Saito, Chie ; Schlom, Jeffrey ; Camphausen, Kevin ; Coleman, C. Norman ; Hodge, James W. / The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 12. pp. 4533-4544.
@article{abfc17d96c604ef5869cf9d402d0b2a3,
title = "The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors",
abstract = "Purpose: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. Experimental Design: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+ suppressor cells. Results: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non - self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). Conclusions: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.",
author = "Chie Kudo-Saito and Jeffrey Schlom and Kevin Camphausen and Coleman, {C. Norman} and Hodge, {James W.}",
year = "2005",
month = "6",
day = "15",
doi = "10.1158/1078-0432.CCR-04-2237",
language = "English (US)",
volume = "11",
pages = "4533--4544",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors

AU - Kudo-Saito, Chie

AU - Schlom, Jeffrey

AU - Camphausen, Kevin

AU - Coleman, C. Norman

AU - Hodge, James W.

PY - 2005/6/15

Y1 - 2005/6/15

N2 - Purpose: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. Experimental Design: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+ suppressor cells. Results: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non - self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). Conclusions: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.

AB - Purpose: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. Experimental Design: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+ suppressor cells. Results: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non - self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). Conclusions: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.

UR - http://www.scopus.com/inward/record.url?scp=20444468485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20444468485&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-04-2237

DO - 10.1158/1078-0432.CCR-04-2237

M3 - Article

C2 - 15958639

AN - SCOPUS:20444468485

VL - 11

SP - 4533

EP - 4544

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 12

ER -