Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France.
PLoS One. 2010 May 4;5(5):e10458. doi: 10.1371/journal.pone.0010458.
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.
Stimulation of PBMC from HLA-A0201(+) donors by HLA-A0201 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.
These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.
开发有效的癌症疫苗仍然是一个挑战。尽管浆细胞样树突状细胞（pDCs）在抗肿瘤反应中起着至关重要的作用，但它们的治疗潜力尚未得到充分发挥。我们探索了与 HLA-A*0201 匹配的同种异体 pDC 作为免疫治疗载体的相关性。
用肿瘤衍生肽脉冲刺激 HLA-A0201(+)供体的 PBMC，可触发 HLA-A0201 匹配的同种异体 pDC 刺激的抗原特异性和功能性细胞毒性 T 细胞反应（高达 98%四聚体(+) CD8 T 细胞）。pDC 疫苗在人源化小鼠模型中表现出强烈的抗肿瘤治疗疗效，抑制肿瘤生长。它还从 I-IV 期黑色素瘤患者的 PBMC 和 TIL 中体外诱导出高度功能性的肿瘤特异性 T 细胞。针对 MelA、GP100、酪氨酸酶和 MAGE-3 抗原的反应达到四聚体水平分别高达 62%、24%、85%和 4.3%。pDC 疫苗诱导的 T 细胞特异性杀伤患者自身的同源黑色素瘤肿瘤细胞。这种半同种异体 pDC 疫苗比传统的髓样树突状细胞疫苗更有效。此外，pDC 疫苗设计赋予其在癌症治疗中具有很强的临床应用潜力。
这些发现强调了与 HLA-A*0201 匹配的同种异体 pDC 作为肿瘤免疫的有效诱导剂，并提供了一种有前途的免疫治疗策略来对抗癌症。
