CCIT, Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital, Herlev, Denmark.
J Transl Med. 2012 Aug 21;10:169. doi: 10.1186/1479-5876-10-169.
Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections.
This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day.
Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3-4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission.
Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.
过继性细胞疗法可能基于肿瘤特异性 T 细胞的分离，例如自体肿瘤浸润淋巴细胞（TIL），在体外激活和扩增，然后在化疗引起的淋巴细胞耗竭后将这些细胞重新输注到患者体内。与大剂量白细胞介素（IL）-2 一起，这种治疗方法已用于晚期恶性黑色素瘤患者，疗效显著，但也观察到与 IL-2 相关的显著毒性。在这里，我们介绍了丹麦转化研究中心使用 TIL 过继转移联合低剂量皮下 IL-2 注射的可行性研究的数据。
这是一项试验性研究（ClinicalTrials.gov 标识符：NCT00937625），包括转移性黑色素瘤、PS ≤1、年龄 <70、可测量和进行性疾病且无中枢神经系统受累的患者。6 例患者接受淋巴细胞耗竭化疗、TIL 输注和 14 天的皮下低剂量 IL-2 注射，2 MIU/天。
低剂量 IL-2 显著降低了治疗相关毒性，没有 3-4 级与 IL-2 相关的不良反应。6 例治疗患者中有 2 例出现客观临床反应，持续完全缓解（30+和 10+个月），2 例稳定疾病（4 和 5 个月），2 例在治疗后不久进展。分析了治疗前后输注细胞和外周淋巴细胞的肿瘤反应性。输注产品中肿瘤特异性 T 细胞的绝对数量与临床反应呈正相关，也观察到 1 例完全缓解患者外周肿瘤反应性 T 细胞的诱导。
采用过继性细胞疗法联合低剂量 IL-2 治疗后，诱导了完全和持久的反应，显著降低了该疗法的毒性。
