Wang Xiaojin, Bayer Michael E, Chen Xiaosong, Fredrickson Craig, Cornforth Andrew N, Liang Greg, Cannon Jessica, He Jia, Fu Qingchun, Liu Jia, Nistor Gabriel I, Cao Wei, Chen Chengwei, Dillman Robert O
Hospital 85 People's Liberation Army of China, Shanghai, China.
J Surg Oncol. 2015 Jun;111(7):862-7. doi: 10.1002/jso.23897. Epub 2015 Apr 14.
Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis-B or -C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long-term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high-risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis.
Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC-TC. After one course of trans-arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC-TC suspended in granulocyte-macrophage colony stimulating factor were administered. Patients were monitored for eight weeks.
HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA.
Autologous DC-TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned.
肝细胞癌（HCC）常与乙型或丙型肝炎病毒引起的慢性肝炎相关。采用来自自体肿瘤干细胞（TC）系的抗原的自体树突状细胞（DC）进行主动特异性免疫治疗（ASI）与转移性癌症患者有希望的长期生存相关，但肝炎患者被排除在外。ASI可能使手术切除后的高危原发性HCC患者受益，但首先重要的是要证明ASI不会加重肝炎。
先前未经治疗的HCC患者，若有一个直径>5 cm的孤立病灶，或三个病灶中至少有一个直径>3 cm，或病灶超过三个，则接受手术切除，并从中建立自体TC系。将经照射的TC与自体DC孵育以产生DC-TC。在进行一个疗程的经动脉化疗栓塞治疗（TACE）后，每周皮下注射三次悬浮于粒细胞-巨噬细胞集落刺激因子中的DC-TC。对患者进行八周的监测。
15例患者中有15例在五周内建立了HCC细胞系。对8例均为慢性乙型肝炎的患者进行了治疗。肝转氨酶、乙型肝炎抗原或病毒DNA均未增加。
自体DC-TC在这些HCC患者中未加重乙肝病毒感染。正在计划进行一项II期疗效试验。
