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PLoS One. 2010 May 4;5(5):e10458. doi: 10.1371/journal.pone.0010458.

A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

Author information

1
Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France. carolineaspord@yahoo.com

Abstract

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.

METHODS AND FINDINGS:

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.

PMID:
20454561
PMCID:
PMC2864288
DOI:
10.1371/journal.pone.0010458
[Indexed for MEDLINE]
Free PMC Article

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