Enhancement of Anti-Telomerase Immunity Against Prostate Cancer
Abstract
The overall objective of this proposal is to enhance the efficacy of cancer vaccines by selectively eliminating or reducing CD4+ regulatory T cells (Treg) expressing the high affinity CD25 IL-2-specific receptor (IL-2R) in patients with metastatic prostate cancer. Preclinical and clinical data from our laboratory (see Reference 1 and Appendix A) and others (2, 3) have shown that CD4+/CD25+ Treg play an important role in the suppression of T cell responses and that elimination of Treg is capable of enhancing T-cell proliferation and cytolytic activity in vitro. We have also demonstrated that human Treg can selectively be depleted in cancer patients using the IL- 2/diphtheria toxin conjugate denileukin diftitox, without inducing toxicity on other cellular subsets with intermediate or low expression of CD25 (1). Most importantly, denileukin diftitox-mediated elimination of Treg followed by vaccination with tumor RNA-transfected DC significantly improved the stimulation of tumorspecific T-cell responses in RCC patients, when compared to vaccination alone. These findings formed the basis of this proposal aimed to augment a vaccine-induced T cell responses by pretreatment of prostate cancer patients with agents that can lead to the preferential depletion of the CD4+/CD25+ regulatory T cells, such as agents which target and kill cells expressing the IL-2 receptor CD25 subunit.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2006
- Accession Number
- ADA463236
Entities
People
- Johannes Vieweg
Organizations
- Duke University Hospital