Feeding dendritic cells with tumor antigens: self-service buffet or à la carte?
Adoptive transfer of autologous dendritic cells (DC) presenting tumor-associated antigens initiate and sustain an immune response which eradicate murine malignancies. Based on these observations, several clinical trials are in progress testing safety and efficacy with encouraging preliminary reports. In these approaches, ex vivo incubation of DC with a source of tumor antigens is required to load the relevant antigenic epitopes on the adequate antigen presenting molecules. Recent data show that in some instances exogenous DC artificially injected into malignant tissue or endogenous DC attracted to the tumor nodule by means of gene transfer of GM-CSF and CD40L into malignant cells result in efficacious antitumor immunity. In the case of intratumoral injection of DC the procedure is curative only if DC had been genetically engineered to produce IL-12, IL-6 or to express CD40L. Evidence has been obtained showing that intratumoral DC can capture and process tumor antigens to be presented to T-lymphocytes. Although the exact mechanisms of tumor antigen acquisition by DC are still unclear, available data suggest a role for heat shock proteins released from dying malignant cells and for the internalization of tumor-derived apoptotic bodies. Roles for tumor necrosis versus apoptosis are discussed in light of the 'danger theory'. Gene Therapy (2000) 7, 1167-1170.
Melero
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Gene Therapy Division, Internal Medicine Department, University of Navarra School of Medicine, Pamplona, Spain.
Vile
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RG
Colombo
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MP
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D012190:Retroviridae / Q000235:genetics
D000951:Antigens, Neoplasm; D016207:Cytokines