Abstract:
Adult T-cell leukemia-lymphoma (ATL) is a highly aggressive peripheral T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1) infection occurring in approximately 5% of patients after prolonged latent period. ATL relapses within a short period despite its transient response to multiagent chemotherapy and the prognosis is extremely poor due to anticancer drug resistance and immunodeficiency. Although novel agents with different mechanisms, such as molecular targeted agents, have improved the prognosis, the number of cured patients remains limited. Hematopoietic stem cell transplantation resulted in long-term remission, whereas its indication is limited due to treatment-related mortality. As most ATL patients are of advanced age, development of a lesser toxic treatment is necessary. Therefore, we developed a novel therapeutic dendritic cell vaccine targeting the HTLV-1 Tax antigen. The safety profile has been confirmed in a pilot and phase I clinical studies, and a promising long-term clinical efficacy has also been obtained. This novel vaccine is a noninvasive, long-lasting therapy for ATL and can potentially be extended to different applications for low-grade ATL and high-risk HTLV-1 carriers.
摘要:
成人T细胞白血病淋巴瘤(ATL)是一种高度侵袭性的外周T细胞肿瘤,由人T细胞白血病病毒1型(HTLV-1)感染引起,约有5%的患者在潜伏期延长后发生。尽管ATL对多药化疗有短暂反应,但在短时间内复发,并且由于抗癌药物耐药性和免疫缺陷,预后极差。虽然具有不同机制的新型药剂,如分子靶向药物,改善了预后,治愈的患者数量仍然有限。造血干细胞移植导致长期缓解,而由于治疗相关的死亡率,其适应症有限。由于大多数ATL患者都是高龄患者,开发毒性较小的治疗方法是必要的。因此,我们开发了一种针对HTLV-1Tax抗原的新型治疗性树突状细胞疫苗。安全性已在试点和I期临床研究中得到证实,并获得了有希望的长期临床疗效。这种新型疫苗是非侵入性的,ATL的长期治疗,可能会扩展到低级别ATL和高风险HTLV-1携带者的不同应用。