CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy.

Published

Journal Article

BACKGROUND: Dendritic cell (DC)-based immunotherapy is a promising form of adjuvant therapy for high-risk tumors. DCs transfected with tumor-associated antigens are capable of stimulating antigen-specific T cells, but cytolytic responses have been disappointing. Activation of DC surface CD40 influences DC cytokine production, particularly that of interleukin (IL)-12, which favors a Th1 (cytotoxic) helper T cell response. This study evaluated the effects of exogenous soluble CD40 ligand (sCD40L) on RNA-transfected DC preparations and their subsequent ability to generate antimelanoma cytolytic T cells. METHODS: Human monocyte-derived DCs were cultured and transfected with mRNA encoding full-length melanoma-associated antigen, Mart-1, and matured with and without sCD40L. DC IL-12 secretion and the ability to stimulate naïve T cells were assessed by enzyme-linked immunosorbent assay (ELISA), tetramer analysis, Elispot, and (51)Cr release assay. RESULTS: Mature DCs stimulated with sCD40L secreted higher levels of IL-12 compared with immature DCs and DCs matured without sCD40L (P <.001). DCs treated with sCD40L generated a greater number of antigen-specific T cells (P <.05) by tetramer and Elispot analyses, and yielded specific T cells with significant cytotoxicity against HLA-matched melanoma cell lines. CONCLUSIONS: CD40L augments DC IL-12 secretion and is essential to potentiate specific antimelanoma cytolytic responses stimulated by the Mart-1 antigen. sCD40L should be considered a crucial adjuvant in DC preparations for RNA-based DC vaccine therapies.

Full Text

Duke Authors

Cited Authors

  • Onaitis, MW; Kalady, MF; Emani, S; Abdel-Wahab, Z; Tyler, DS; Pruitt, SK

Published Date

  • August 2003

Published In

Volume / Issue

  • 134 / 2

Start / End Page

  • 300 - 305

PubMed ID

  • 12947333

Pubmed Central ID

  • 12947333

International Standard Serial Number (ISSN)

  • 0039-6060

Digital Object Identifier (DOI)

  • 10.1067/msy.2003.240

Language

  • eng

Conference Location

  • United States