Targeting dendritic cells with antigen-containing stealth liposomes in vivo. Dendritic cells (DCs) pulsed with tumor antigen ex vivo have applications in tumor immunotherapy, but their isolation from patients, ex vivo culture, pulsing with antigen, and re-introduction into patients can be impractical. The cover shows how this difficulty could be overcome. Left panel: Structure of a novel metal chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA₃-DTDA). Right panel: Stealth liposomes containing NTA₃-DTDA can be conveniently engrafted with a histidine-tagged targeting protein. Using antigen-containing stealth liposomes engrafted with single chain antibody fragments to markers on DCs, the authors show that antigen can be targeted directly to DCs in vivo. Use of the liposomes as a vaccine in syngeneic mice induced strong anti-tumor responses and a dramatic therapeutic effect, against the highly metastatic murine melanoma, B16-OVA, prolonging disease-free survival. Similarly, plasma membrane vesicles derived from B16-OVA cells also could be modified for targeting to DCs. The effectiveness of the vaccines was dependent on the simultaneous delivery of antigen and a DC maturation/danger signal (interferon- or lipopolysaccharide). The targeting of antigen to DCs in this way could be an effective procedure for enhancing tumor immunity and for immunotherapy. Future studies will test this approach in patients with metastatic melanoma. For details, see the article by Broekhoven et al. on page 4357 of this issue.