Accession Number:

ADA463236

Title:

Enhancement of Anti-Telomerase Immunity Against Prostate Cancer

Descriptive Note:

Annual rept. 15 Oct 2005-14 Oct 2006

Corporate Author:

DUKE UNIV MEDICAL CENTER DURHAM NC

Personal Author(s):

Report Date:

2006-11-01

Pagination or Media Count:

18.0

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 CD4CD25 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- 2diphtheria 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 CD4CD25 regulatory T cells, such as agents which target and kill cells expressing the IL-2 receptor CD25 subunit.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE