Palucka A Karolina, Dhodapkar Madhav V, Paczesny Sophie, Ueno Hideki, Fay Joseph, Banchereau Jacques
Baylor Institute for Immunology Research, Dallas, Texas 75204, USA.
J Immunother. 2005 Mar-Apr;28(2):158-68. doi: 10.1097/01.cji.0000154249.74383.17.
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.
基于树突状细胞（DC）的疫苗的免疫原性已在晚期癌症患者中得到证实，但引发的癌症特异性免疫是否持久以及是否可以通过加强接种来维持，目前尚未明确。作者早些时候在18名HLA-A*0201转移性黑色素瘤患者中发现，在6周内进行四次负载肽的CD34-DC疫苗接种（诱导期）后，血液中的黑色素瘤特异性CD8+ T细胞会扩增，这通过黑色素瘤肽特异性IFN-γ ELISPOT以及针对黑色素瘤细胞系的细胞毒性T淋巴细胞（CTL）活性得以证实。作者在此表明，黑色素瘤肽特异性CD8+ T细胞免疫是短暂的，但在11名接受四次负载肽的CD34-DC加强接种的患者中，有7名患者的这种免疫能够被重新激活。通过四聚体结合以及针对黑色素瘤肽脉冲T2细胞的CTL活性证实了记忆性CD8+ T细胞的扩增。在两名接受超过15个月加强接种的患者中，诱导产生的黑色素瘤肽特异性记忆性CD8+ T细胞持续了至少6个月。因此，用负载肽的CD34-DC进行加强接种可以扩展长期存在的肿瘤肽特异性免疫。
