Enhanced migration of human dendritic cells expressing inducible CD40.

Abstract

Dendritic cells (DC) are the most potent antigen-presenting cells for priming and activating naïve CD4(+) and CD8(+) T lymphocytes. This property has led to their use as a cellular vaccine in a number of clinical trials with promising results. However, the clinical efficacy of DC vaccines in patients has been unsatisfactory, probably because of a number of key deficiencies, including limited migration of ex vivo generated DCs to the secondary lymphoid tissues. To enhance human DC-based vaccines, we used the combination of an inducible CD40 receptor (iCD40) along with TLR-4 ligation. The iCD40 receptor permits targeted, reversible activation of CD40. Using iCD40 in combination with lipopolysaccharides (LPS), we enhanced DCs migration in vitro upon escalation of the AP1903 dimerizer drug doses. This result suggests that the use of iCD40-modified and LPS-stimulated DCs is a potent strategy in DC-based cancer immunotherapies.