Department of Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), Peking University School of Oncology/Beijing Cancer Hospital and Institute, 52 Fucheng Rd, Beijing, 100142, China.
Clin Transl Oncol. 2012 Sep;14(9):675-81. doi: 10.1007/s12094-012-0854-7. Epub 2012 Jul 19.
The aim of the study is to explore the safety of cytotoxic T lymphocytes (CTLs) infusion by transfected dendritic cells (DCs) with recombinant adeno-associated virus vector (rAAV) carrying CEA cDNA among advanced cancer patients.
A total of 27 cancer patients with tumor tissue expression positivity and/or sera-elevated level of CEA were subsequently divided into cohort A and B resulted from the ex vivo expansion number of CTLs generated from co-culture of specific transfected DCs with autologous T lymphocytes. Based on the variations of infused number of specific CTL derived from different yields of individualized patients who had experienced various anti-cancer treatments, we compared the patients of low number of CTL cells (2-8 × 10(8) infused, cohort A, 6 cases) with those of higher number (above 8 × 10(8) infused, cohort B, 21 cases) to testify the possible adverse reactions caused by amount of infused CTLs. This study resembled a phase I study aiming for setting up clinical trial of adoptive cellular therapy that conceptually comes from conventional cytotoxic drugs.
The results showed that one case from the each cohort had experienced moderate fever, and four cases with fatigue were seen in cohort B. The symptoms were transient without serious adverse events. For the consideration of clinical response 2 partial remission (8.0 %, 2/25), 1 minor remission, and 9 stable disease (40 %, 10/25) were observed in 25 patients eligible for evaluation. Sera levels of CEA assay were lowered in six patients. During a median follow-up of 8.1 months, we could not observe severe or chronic adverse reactions related to rAAV-DC infusions. Meanwhile, the variation of number of CTLs infused in this setting did not alter the status of peripheral lymphocyte population.
These preliminary data suggest that the rAAV-DC immunotherapy is well-tolerated and showed no severe adverse reactions in cancer patients.
本研究旨在探讨转染重组腺相关病毒载体（rAAV）携带 CEA cDNA 的树突状细胞（DC）输注细胞毒性 T 淋巴细胞（CTLs）在晚期癌症患者中的安全性。
共 27 例肿瘤组织表达阳性和/或 CEA 血清水平升高的癌症患者随后分为 A 组和 B 组，这两组是根据从特异性转染的 DC 与自体 T 淋巴细胞共培养中产生的 CTL 的体外扩增数量来划分的。基于接受不同数量个体化患者来源的特异性 CTL 输注后数量的变化，我们比较了 CTL 细胞数量较低的患者（输注量为 2-8×10^8，A 组，6 例）与 CTL 细胞数量较高的患者（输注量大于 8×10^8，B 组，21 例），以验证输注 CTL 数量可能引起的不良反应。这项研究类似于 I 期临床试验，旨在建立源于传统细胞毒性药物的过继细胞治疗的临床试验概念。
结果显示，A 组中每个队列都有 1 例患者出现中度发热，B 组中有 4 例患者出现疲劳。这些症状是短暂的，没有严重的不良事件。在 25 例可评估的患者中，观察到 2 例部分缓解（8.0%，2/25），1 例轻微缓解，9 例稳定疾病（40%，10/25）。6 例患者的 CEA 检测血清水平降低。在中位随访 8.1 个月期间，我们未观察到与 rAAV-DC 输注相关的严重或慢性不良反应。同时，在此设置下输注 CTLs 的数量变化并未改变外周淋巴细胞群的状态。
这些初步数据表明，rAAV-DC 免疫疗法在癌症患者中耐受良好，未观察到严重不良反应。
