Antigen trapping by dendritic cells for antitumor therapy
ABSTRACT
Dendritic cells (DC) are potent antigen-presenting cells (APC) that are capable of stimulating both naive CD4(+) T helper cells and CD8(+) cytotoxic T cells. Therefore, DC are being extensively evaluated as vehicles for antigen delivery in immunotherapies for the treatment of patients with cancer. Many techniques have been used to load DC with tumor-associated antigens (TAA), including pulsing with synthetic peptides that represent T cell epitopes. This strategy has been used in several human clinical vaccination trials; however, it is limited to patients who express the particular peptide MHC-restricting molecule. Alternatively, DC have been pulsed with recombinant proteins or transduced with recombinant viruses. These approaches circumvent the MHC restrictions associated with peptides but are generally limited to individual proteins. Because many tumors display heterogenous expression of target antigens, strategies that induce T cell responses against multiple proteins may be more efficacious. Another concern is that some of these antigen-loading techniques facilitate the presentation of immunogenic viral or bacterial epitopes in addition to those from the tumor-associated protein.