Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses

Chie Kudo-Saito, Jeffrey Schlom, James W. Hodge

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Purpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimalatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication- competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects. Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA+ tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed. Results: In CEA+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA+ tumor after therapy was specific for gp70. Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.

Original languageEnglish
Pages (from-to)2416-2426
Number of pages11
JournalClinical Cancer Research
Volume11
Issue number6
DOIs
Publication statusPublished - 2005 Mar 15
Externally publishedYes

Fingerprint

Carcinoembryonic Antigen
Vaccination
Antigens
T-Lymphocytes
Neoplasms
Fowlpox
Vaccinia
Cancer Vaccines
Neoplasm Antigens
Vaccines
B7 Antigens
Poxviridae
Therapeutic Uses
Intercellular Adhesion Molecule-1
Transgenes
Transgenic Mice
Epitopes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses. / Kudo-Saito, Chie; Schlom, Jeffrey; Hodge, James W.

In: Clinical Cancer Research, Vol. 11, No. 6, 15.03.2005, p. 2416-2426.

Research output: Contribution to journalArticle

Kudo-Saito, Chie ; Schlom, Jeffrey ; Hodge, James W. / Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 6. pp. 2416-2426.
@article{5ff0eb8e93034965852ec3659c2a8a56,
title = "Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses",
abstract = "Purpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimalatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication- competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects. Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA+ tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed. Results: In CEA+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA+ tumor after therapy was specific for gp70. Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.",
author = "Chie Kudo-Saito and Jeffrey Schlom and Hodge, {James W.}",
year = "2005",
month = "3",
day = "15",
doi = "10.1158/1078-0432.CCR-04-1380",
language = "English",
volume = "11",
pages = "2416--2426",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses

AU - Kudo-Saito, Chie

AU - Schlom, Jeffrey

AU - Hodge, James W.

PY - 2005/3/15

Y1 - 2005/3/15

N2 - Purpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimalatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication- competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects. Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA+ tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed. Results: In CEA+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA+ tumor after therapy was specific for gp70. Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.

AB - Purpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimalatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication- competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects. Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA+ tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed. Results: In CEA+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA+ tumor after therapy was specific for gp70. Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.

UR - http://www.scopus.com/inward/record.url?scp=16844362403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16844362403&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-04-1380

DO - 10.1158/1078-0432.CCR-04-1380

M3 - Article

C2 - 15788693

AN - SCOPUS:16844362403

VL - 11

SP - 2416

EP - 2426

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 6

ER -