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 naïve 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 naïve CTL, and (iii) protect against B16.OVA challenge. Peptide-pulsed autologous and allogeneic DC were also tested in naïve 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 naïve CTL priming and tumour protection. Autologous human DC were similarly more potent at naïve CTL priming against the melanoma-associated TAA MART-1 in vitro.


CONCLUSIONS
The expression of allogeneic MHC antigens on peptide-pulsed DC impairs naïve CTL priming and anti-tumour effects, despite effective TAA presentation both in vitro and in vivo.
Cancer Research UK Clinical Centre, St James's University Hospital, Beckett St, Leeds LS9 7TF, UK. a.merrick@leeds.ac.uk
Alison
A
Merrick
Rosa Maria
RM
Diaz
Dearbhaile
D
O'Donnell
Peter
P
Selby
Richard
R
Vile
Alan
A
Melcher
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D006649:Histocompatibility Antigens / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006649:Histocompatibility Antigens; D010455:Peptides