Intratumoral Vaccination and Diversified Subcutaneous/Intratumoral Vaccination with Recombinant Poxviruses Encoding a Tumor Antigen and Multiple Costimulatory Molecules

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Purpose: Intratumoral (i.t.) vaccination represents a potential modality for the therapy of tumors. Previous i.t. vaccination studies have focused on the efficacy of i.t. vaccination alone. There are no reports that clearly compared i.t. vaccination with systemic vaccination achieved by s.c., lntradermal, or i.m. injection, or combining both modalities of systemic and i.t. vaccination. Here, we compared the antitumor effects induced by a systemic vaccination regimen (s.c.) and i.t. vaccination, and a sequential s.c/i.t. vaccination regimen. In this study, we used a recombinant vaccinia virus containing the transgenes for carcinoembryonic antigen (CEA) and a triad of T-cell costimulatory molecules (B7-1, ICAM-1, and LFA-3; designated rV-CEA/TRICOM) for s.c. priming and a replication defective avipox (fowlpox) virus containing the same four transgenes (designated rF-CEA/TRICOM) for i.t. vaccination or s.c. booster vaccinations. Experimental Design: Vaccination was started on day 8 after s.c. implantation with CEA-positive tumors. We compared the antitumor activity induced by these vaccines when administered via the i.t. route versus the s.c. route. Subsequent therapy studies examined the sequential combination of these routes, s.c. priming with rV-CEA/TRICOM followed by i.t. boosting with rF-CEA/TRICOM. Initial studies were conducted in conventional mice to define optimal vaccine regimens and then in CEA-transgenic mice that expressed CEA as a "self" antigen in a manner similar to that of an advanced colorectal cancer patient. Results: The results demonstrate that the antitumor activity induced by i.t. vaccination is superior to that induced by s.c. vaccination. For more advanced tumors, a s.c. priming vaccination, followed by i.t. boosting vaccinations was superior to either s.c. or i.t. vaccination alone. Both of these phenomena were observed in tumor models where the tumor-associated antigen is a foreign antigen and in a CEA-transgenic tumor model where the tumor-associated antigen is a self-antigen. The cytokine, granulocyte macrophage colony-stimulating factor admixed in vaccines, was shown to be essential in inducing the antitumor activity. Conclusions: These studies demonstrate that the diversified vaccine regimens that consisted of s.c. prime and i.t. boosts with CEA/TRICOM vectors could induce antitumor therapy superior to that seen by either route alone.

Original languageEnglish
Pages (from-to)1090-1099
Number of pages10
JournalClinical Cancer Research
Volume10
Issue number3
DOIs
Publication statusPublished - 2004 Feb 1
Externally publishedYes

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Poxviridae
Neoplasm Antigens
Vaccination
Carcinoembryonic Antigen
Vaccines
Autoantigens
Neoplasms
Transgenes
Fowlpox virus
CD80 Antigens
CD58 Antigens
Vaccinia virus

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Intratumoral Vaccination and Diversified Subcutaneous/Intratumoral Vaccination with Recombinant Poxviruses Encoding a Tumor Antigen and Multiple Costimulatory Molecules. / Kudo-Saito, Chie; Schlom, Jeffrey; Hodge, James W.

In: Clinical Cancer Research, Vol. 10, No. 3, 01.02.2004, p. 1090-1099.

Research output: Contribution to journalArticle

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