Tumor lysate versus peptide loaded dendritic cell vaccination strategies for active cancer immunotherapy.

Abstract

Dendritic cells (DCs) have been exploited for use in tumor immunotherapy due to their unique ability to efficiently prime tumor specific T cells <italic> in vivo</italic>. Recent work has shown that using tumor lysate-pulsed DCs (TL-DCs) is more effective in treating established tumors than peptide-pulsed (PP) DC-based vaccines. We compared the capacity of these two vaccination strategies to elicit anti-tumor T cell responses <italic>in vitro</italic> and <italic>in vivo</italic> using the murine B16 melanoma model. DCs prepared from bone marrow cultures containing GM-CSF and IL-4 were endocytic, and expressed MHC and co-stimulatory molecules necessary for priming of naive T cells. Exposure of these DCs to necrotic B16 tumor lysate did not induce DC maturation. Vaccination with DCs loaded with tumor lysate or an MHC class I-restricted melanoma peptide (TRP2_180--188or hgp100_25--33) promoted protective anti-tumor immunity. These results were associated with the elicitation of IFNgamma and cytotoxic tumor-specific T cell responses. TL-DC immunization promoted priming not restricted to defined MHC class I-restricted immunodominant epitopes, and also targeted the CD4<super>+</super> T cell compartment. These findings suggest that eliciting a broader tumor-specific T cell response with TL-DC vaccination, may confer an enhanced ability to treat established tumors when compared to PP-DC vaccination strategies.