Enhancement of Anti-Telomerase Immunity Against Prostate Cancer
Abstract
The major objective of this proposal is to enhance the efficacy of specific active immunotherapy (SAI) by selectively eliminating or reducing CD4+ regulatory T cells (T(sub reg))1 in patients with metastatic prostate cancer. Preclinical and clinical data from our laboratory have shown that CD4+ and CD25+ co-expressing T(sub reg) play an important role in the suppression of T cell responses in the cancer patient. Moreover, we have demonstrated that elimination of T(sub reg) is capable of enhancing T-cell proliferation and cytolytic activity in vitro. A recent report previously suggested that human T(sub reg) 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. Most importantly, denileukin diftitox-mediated elimination of T(sub reg) 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 (Appendix A). Cumulatively, these findings formed the basis of performing a clinical study in which the T(sub reg) depletion strategy was tested in patients with metastatic prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2007
- Accession Number
- ADA486611
Entities
People
- Johannes Vieweg
Organizations
- Duke University Hospital