Autologous versus allogeneic peptide-pulsed dendritic cells for anti-tumour vaccination: expression of allogeneic MHC supports activation of antigen specific T cells, but impairs early naive cytotoxic priming and anti-tumour therapy

Background Dendritic cells (DC) pulsed with MHC class I-restricted tumour associated antigen (TAA) peptides have been widely tested in pre-clinical models and early clinical studies for their ability to prime cytotoxic T cell (CTL) responses. The effect of co-expression of allogeneic MHC antigens on DC immunogenicity has not been addressed, and has implications for the feasibility of clinical applications. Objective This study compared DC from autologous H-2(b) or semi-allogeneic F1 H-2(bxk) mice pulsed with the H-2(b)-restricted model ovalbumin (OVA) peptide SIINFEKL, and compared in vitro and in vivo their ability to (i) activate specific OT1 cells, (ii) prime naive CTL, and (iii) protect against B16.OVA challenge. Peptide-pulsed autologous and allogeneic DC were also tested in naive human CTL priming assays. Results Semi-allogeneic DC expressed higher levels of co-stimulatory molecules. On pulsing with SIINFEKL they triggered greater proliferation of OT1 cells in vitro and in vivo, but were less effective at naive CTL priming and tumour protection. Autologous human DC were similarly more potent at naive CTL priming against the melanoma-associated TAA MART-1 in vitro. Conclusion The expression of allogeneic MHC antigens on peptide-pulsed DC impairs naive CTL priming and antitumour effects, despite effective TAA presentation both in vitro and in vivo.