Preclinical Evaluation of Novel Dendritic Cell-Based Prostate Cancer Vaccines
Annual summary rept. 1 Jan-31 Dec 2007
BAYLOR COLL OF MEDICINE HOUSTON TX
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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.
- Medicine and Medical Research