A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.
BACKGROUND
The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy.


RESULTS
Stimulation of PBMC from HLA-A*0201(+) donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+) CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment.


CONCLUSIONS
These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.
Aspord
Caroline
C
Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France. carolineaspord@yahoo.com
Charles
Julie
J
Leccia
Marie-Therese
MT
Laurin
David
D
Richard
Marie-Jeanne
MJ
Chaperot
Laurence
L
Plumas
Joel
J
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006262:Health; D006650:Histocompatibility Testing; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009367:Neoplasm Staging; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014019:Tissue Donors; D014611:Vaccination
D019496:Cancer Vaccines; D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides
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