Accession Number:

ADA409632

Title:

Effect of Tumor Derived TGF-Beta on the Efficacy of Dendritic Cell Vaccines

Descriptive Note:

Annual summary 1 Jul 2001-30 Jun 2002

Corporate Author:

ARIZONA UNIV TUCSON

Report Date:

2002-07-01

Pagination or Media Count:

38.0

Abstract:

Dendritic cell DC-based vaccines have exhibited minimal effectiveness in treating established tumors, likely due to factors present in the tumor microenvironment. One such factor is Transforming Growth Factor - beta TGF-beta, a cytokine which is produced by numerous tumor types and has been demonstrated to impair DC functions in vitro. We have evaluated the effect of TGF-beta on the immunostimulatory activities of DCs. We demonstrate that TGF-beta exposure inhibits the ability of DCs to present antigen, stimulate tumor- sensitized T lymphocytes, and migrate to draining lymph nodes. Neutralization of TGF-beta using the TGF-beta neutralizing antibody, 2G7 enhanced the ability of DC vaccines to inhibit the growth of established 4T1 murine mammary tumors. Treatment of 4T1 tumors transduced with the antisense TGF-beta transgene 4T1- asT with the combination of DC and 2G7 antibody inhibited tumor growth and resulted in complete regression of tumors in 40 of the mice. These results demonstrate that neutralization of TGF-beta in tumor-bearing mice enhances the efficacy of DC-based vaccines,

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE