Boosting vaccinations with peptide-pulsed CD34+ progenitor-derived dendritic cells can expand long-lived melanoma peptide-specific CD8+ T cells in patients with metastatic melanoma.
The immunogenicity of dendritic cell (DC)-based vaccines has been shown in patients with advanced cancer, but it has not yet been established whether the elicited cancer-specific immunity is durable and whether it can be maintained by boosting vaccinations. The authors showed earlier, in 18 HLA-A*0201 metastatic melanoma patients, that four vaccinations over 6 weeks with peptide-loaded CD34-DCs (the induction phase) expand in the blood melanoma-specific CD8+ T cells, as documented by melanoma peptide-specific IFN-gamma ELISPOT and cytotoxic T-lymphocyte (CTL) activity against melanoma cell lines. The authors show here that the melanoma peptide-specific CD8+ T-cell immunity is short-lived, but it could be reactivated in 7 of 11 patients who received four boosting vaccinations with peptide-loaded CD34-DCs. Expansion of recall memory CD8+ T cells was confirmed by tetramer binding and CTL activity against melanoma peptide-pulsed T2 cells. In two patients boosted over 15 months, induced melanoma peptide-specific recall memory CD8+ T cells lasted at least 6 months. Thus, boosting vaccination with peptide-loaded CD34-DCs can expand long-lived tumor peptide-specific immunity.
Palucka
A Karolina
AK
Baylor Institute for Immunology Research, Dallas, Texas 75204, USA.
Dhodapkar
Madhav V
MV
Paczesny
Sophie
S
Ueno
Hideki
H
Fay
Joseph
J
Banchereau
Jacques
J
D018952:Antigens, CD34 / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry; D013997:Time Factors
D018952:Antigens, CD34; D019496:Cancer Vaccines; D010455:Peptides; D007371:Interferon-gamma