TY - JOUR
T1 - Autologous versus allogeneic peptide-pulsed dendritic cells for anti-tumour vaccination
T2 - Expression of allogeneic MHC supports activation of antigen specific T cells, but impairs early naïve cytotoxic priming and anti-tumour therapy
AU - Merrick, Alison
AU - Diaz, Rosa Maria
AU - O'Donnell, Dearbhaile
AU - Selby, Peter
AU - Vile, Richard
AU - Melcher, Alan
N1 - Funding Information:
Acknowledgments Grant support: Supported by the Medical Research Council, Cancer Research UK, Mayo Foundation and NIH grants RO1 CA85931 and RO1 CA94180.We are grateful to Tim Kottke, Jill Thompson and staff at Biological Resources, Cancer Research UK laboratories (Clare Hall), for technical assistance.
PY - 2008/6
Y1 - 2008/6
N2 - 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-2b or semi-allogeneic F1 H-2bxk mice pulsed with the H-2b-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. Conclusion: 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.
AB - 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-2b or semi-allogeneic F1 H-2bxk mice pulsed with the H-2b-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. Conclusion: 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.
KW - Cancer immunotherapy
KW - Cancer vaccines
KW - Dendritic cells
KW - Tumour-associated antigens
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U2 - 10.1007/s00262-007-0426-9
DO - 10.1007/s00262-007-0426-9
M3 - Article
C2 - 18057935
AN - SCOPUS:43349105987
VL - 57
SP - 897
EP - 906
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 6
ER -