Accession Number:

ADA481556

Title:

Preclinical Evaluation of Novel Dendritic Cell-Based Prostate Cancer Vaccines

Descriptive Note:

Annual summary rept. 1 Jan-31 Dec 2007

Corporate Author:

BAYLOR COLL OF MEDICINE HOUSTON TX

Personal Author(s):

Report Date:

2008-01-01

Pagination or Media Count:

23.0

Abstract:

To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor iCD40 along with TLR-4 ligation in human monocyte-derived DCs. The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4 T cells for activation of DCs. As a rigorous preclinical study of this approach, we evaluated key parameters of DC activation and function. While neither iCD40 nor TLR4 signaling alone led to high levels of IL-12p70 and IL-6, using iCD40 in combination with lipopolysaccharides LPS led to strongly synergistic production of both. Furthermore, this approach led to high expression of DC maturation markers, epitope-specific cytotoxic T cell and TH1 responses, as well as DC migration in vitro. Moreover, use of iCD40-modified and LPS-stimulated DCs led to targeted expansion of autologous T cells against the attractive tumor-associated antigen, prostate-specific membrane antigen PSMA, supporting this technology as a potent strategy for DC-based prostate cancer immunotherapy.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE