Effect of Tumor Derived TGF-Beta on the Efficacy of Dendritic Cell Vaccines
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,
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA409632
Entities
People
- Emmanuel T. Akporiaye
- James J. Kobie
Organizations
- University of Arizona