Artificial human antigen‐presenting cells are superior to dendritic cells at inducing cytotoxic T‐cell responses

Summary Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes ( CTL s) leads to the killing of cancer cells. A potential challenge for T‐cell immunotherapy is that dendritic cells ( DC s) are exposed to the MHC class I–peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T‐cell response, we generated artificial antigen‐presenting cells ( aAPC s) by incubating human immature DC s (im DC s) with poly(lactic‐co‐glycolic) acid nanoparticles ( PLGA ‐ NP s) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen‐specific CTL s were then induced using either peptide‐loaded mature DC s ( mDC s) or aAPC s, and their activities were analysed using both ELIS pot and cytotoxicity assays. We found that the aAPC s induced significantly stronger tumour antigen‐specific CTL responses than the controls, which included both mDC s and aAPC s loaded with empty nanoparticles. Moreover, frozen CTL s that were generated by exposure to aAPC s retained the capability to eradicate HLA ‐A2‐positive tumour antigen‐bearing cancer cells. These results indicated that aAPC s are superior to DC s when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPC s with PLGA ‐ NP s encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials.