Department of Haematology, National Kyushu Cancer Centre, Fukuoka, Japan.
Br J Haematol. 2015 May;169(3):356-67. doi: 10.1111/bjh.13302. Epub 2015 Jan 22.
Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate- to high-risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax-specific CTL responses were observed with peaks at 16-20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL.
成人 T 细胞白血病/淋巴瘤 (ATL) 是一种人类 T 细胞白血病病毒 I 型 (HTLV-I) 感染的 T 细胞恶性肿瘤,预后较差。我们在此开发了一种新型治疗性疫苗,旨在增强已被证实具有抗 ATL 作用的 HTLV-I Tax 特异性细胞毒性 T 淋巴细胞 (CTL) 反应,并进行了一项初步研究以评估其安全性和疗效。三名曾接受过治疗的 ATL 患者被归类为中高危患者,他们接受了皮下注射该疫苗,该疫苗由与 CTL 表位相对应的 Tax 肽脉冲的自体树突状细胞 (DC) 组成。在所有患者中,接种疫苗后,体能状态均得到改善,无严重不良事件发生,并且在 16-20 周时观察到 Tax 特异性 CTL 反应。两名患者在第 8 周内达到部分缓解,其中一名患者后来获得完全缓解,在接种疫苗后 24 个月和 19 个月时分别无需任何额外化疗而保持缓解状态。第三位患者在活检时其肿瘤细胞缺乏表达 Tax 的能力,在第 8 周内获得稳定疾病,随后虽然无需额外治疗,但病情仍逐渐进展,在接种疫苗后 14 个月时仍在进行。这项初步研究的临床结果表明,Tax 肽脉冲 DC 疫苗是一种安全且有前途的 ATL 免疫疗法。