Dipartimento di Scienze Pediatriche, Università di Pavia, Italy.
Cytotherapy. 2012 Jan;14(1):80-90. doi: 10.3109/14653249.2011.610303. Epub 2011 Sep 23.
Adoptive T-cell therapy with tumor-specific T cells has emerged as a potentially useful approach for treating patients with advanced malignancies. We have demonstrated previously the feasibility of obtaining large numbers of autologous anti-tumor-specific cytotoxic T lymphocytes (CTL) generated by stimulation of patients' peripheral blood mononuclear cells with dendritic cells pulsed with apoptotic tumor cells. Methods. Six patients with progressing metastatic solid tumors (one renal cell carcinoma, two ovarian cancers, two extraosseous peripheral neuroectodermal tumors, one soft tissue sarcoma) not eligible for conventional therapies were treated with adoptive immunotherapy. Anti-tumor CTL, proven to be reactive in vitro against patient tumor cells, but not against normal cells, were infused following lymphodepleting chemotherapy administered to favor T-cell proliferation in vivo.
Patients received a median of nine CTL infusions (range 2-19). The median number of CTL administered per infusion was 11 × 10(8) (range 1-55 × 10(8)). No patient experienced acute or late adverse events related to CTL infusion, even when large numbers of cells were given. Post-infusion laboratory investigations demonstrated an increase in the frequency of circulating anti-tumor T-cells and, in patients with a longer follow-up receiving two CTL infusions/year, a stabilization of these values.
Our study demonstrates that autologous ex vivo-generated anti-tumor CTL can be administered safely in patients with advanced solid tumors and can improve the immunologic reactivity of recipients against tumor. These preliminary results provide a rationale for evaluating the clinical efficacy of this immunotherapeutic approach in phase I/II studies.
过继性 T 细胞疗法利用肿瘤特异性 T 细胞已成为治疗晚期恶性肿瘤患者的一种有前途的方法。我们之前已经证明，通过用凋亡肿瘤细胞脉冲处理树突状细胞来刺激患者外周血单核细胞，获得大量自体抗肿瘤特异性细胞毒性 T 淋巴细胞（CTL）是可行的。方法。六名患有进展性转移性实体瘤（一名肾细胞癌、两名卵巢癌、两名骨外外周神经外胚层肿瘤、一名软组织肉瘤）的患者不符合常规治疗条件，接受了过继性免疫治疗。过继免疫疗法输注的抗肿瘤 CTL 已被证明在体外对患者肿瘤细胞具有反应性，但对正常细胞无反应，在给予有利于体内 T 细胞增殖的淋巴细胞耗竭化疗后输注。
患者接受了中位数为 9 次 CTL 输注（范围 2-19）。每次输注给予的 CTL 中位数为 11×10（8）（范围 1-55×10（8））。即使给予大量细胞，也没有患者出现与 CTL 输注相关的急性或迟发性不良事件。输注后实验室检查显示循环抗肿瘤 T 细胞的频率增加，在接受两年两次 CTL 输注/年的随访时间较长的患者中，这些值稳定。
我们的研究表明，自体体外生成的抗肿瘤 CTL 可以安全地输注到晚期实体瘤患者中，并可以提高受者对肿瘤的免疫反应性。这些初步结果为在 I/II 期研究中评估这种免疫治疗方法的临床疗效提供了依据。
