Targeting dendritic cells with antigen-containing liposomes: antitumour immunity

Abstract

Dendritic cells (DCs) are antigen-presenting cells that play an important role in the body's immune defence against cancer. Strategies using antigen-primed DCs as tumour vaccines show promise in patients, but the approach is cumbersome to use clinically. Soluble tumour antigens can be targeted to DCs in vivo, but this often induces antigenic tolerance rather than immunity. Liposomes are vesicular lipid structures with adjuvant-like properties. Importantly, liposomes can encapsulate antigen and immunomodulatory factors, thus serving as potent delivery vehicles. Different strategies are being explored to target liposomal antigens to DCs in vivo. One approach has employed single-chain antibody fragments to the DC surface molecules CD11c and DEC-205, attached to the vesicle surface by metal-chelating linkage, to target liposomal membranes containing antigen and either interferon-gamma or lipopolysaccharide to DCs. Such membranes induce dramatic antitumour responses and immunotherapeutic effects when used as a vaccine in the murine tumour model B16-OVA melanoma. Liposomal targeting of antigen and maturation signals directly to DCs in vivo, therefore, represents a much simpler strategy for cancer immunotherapy than antigen loading DCs ex vivo.