文章：

过继细胞转移疗法治疗癌症患者

Adoptive-cell-transfer therapy for the treatment of patients with cancer

原文发布日期：2003-09-01

DOI: 10.1038/nrc1167

类型: Review Article

开放获取: 否

要点：

1. Adoptive-cell-transfer (ACT) therapy for patients with cancer relies on the ex vivo generation of highly active, tumour-specific lymphocytes, and their administration in large numbers to the autologous host.
2. Preclinical models have identified characteristics of lymphocyte cultures that are required for successful ACT therapy. The most important characteristic is the presence of high affinity, tumour-antigen-specific CD8⁺ T cells. There is generally a direct correlation between treatment efficacy and the number of transferred, tumour-specific cells.
3. Preclinical models have also identified ways to manipulate the host immune environment that increase ACT therapeutic efficacy. These include immunosuppression before cell administration and concurrent interleukin 2 administration with the transferred T cells.
4. ACT therapy directed at viral antigens has been effective for elimination of Epstein–Barr virus (EBV)-induced post-transplant lymphoproliferative disease. EBV-specific lymphocyte cultures suitable for ACT therapy were generated by repetitive in vitro stimulation using EBV-transformed lymphoblastoid lines.
5. Lymphocyte cultures that were selected for reactivity against melanoma antigens, including melanocyte-differentiation antigens, mediated cancer regression in some patients with metastatic melanoma. Melanoma-reactive cultures that were suitable for ACT therapy were generated from tumour-infiltrating lymphocytes that were rapidly expanded with anti-CD3 antibody.
6. The generation of tumour-antigen-specific lymphocyte cultures is evolving rapidly, spurred on by the identification of tumour antigens and the T-cell receptors that recognize them.
7. Further improvements to ACT therapy will depend on a deeper understanding of basic immunological processes, including the role of CD4⁺ T cells in the antitumour inflammatory response, the ability of lymphocytes to persist in vivo and travel to tumours, and the mechanisms of ACT augmentation by previous host immunosuppression.

要点翻译：

1. 癌症患者的过继性细胞移植（ACT）疗法依赖于体外培养高活性、肿瘤特异性淋巴细胞，并将其大量回输至自体宿主。
2. 临床前模型已明确成功实施ACT疗法所需的淋巴细胞培养物特征。其中最重要的特征是存在高亲和力、肿瘤抗原特异性CD8+T细胞。治疗效果与回输的肿瘤特异性细胞数量通常呈正相关。
3. 临床前模型还揭示了增强ACT疗效的宿主免疫环境调控方法，包括细胞回输前的免疫抑制处理，以及回输T细胞时联用白细胞介素2。
4. 针对病毒抗原的ACT疗法已能有效清除EB病毒（EBV）诱导的移植后淋巴增殖性疾病。适用于ACT疗法的EBV特异性淋巴细胞培养物是通过EBV转化淋巴母细胞系进行重复体外刺激而获得的。
5. 经筛选对黑色素瘤抗原（包括黑素细胞分化抗原）具有反应性的淋巴细胞培养物，在部分转移性黑色素瘤患者中介导了肿瘤消退。适用于ACT疗法的黑色素瘤反应性培养物源自经抗CD3抗体快速扩增的肿瘤浸润淋巴细胞。
6. 随着肿瘤抗原及其识别T细胞受体的发现，肿瘤抗原特异性淋巴细胞培养物的制备技术正在快速发展。
7. ACT疗法的进一步改进有赖于对基础免疫过程的深入理解，包括CD4+T细胞在抗肿瘤炎症反应中的作用、淋巴细胞在体内持续存在及归巢至肿瘤的能力，以及宿主预先免疫抑制增强ACT疗效的机制。

英文摘要：

Adoptive immunotherapy — the isolation of antigen-specific cells, their ex vivo expansion and activation, and subsequent autologous administration — is a promising approach to inducing antitumour immune responses. The molecular identification of tumour antigens and the ability to monitor the persistence and transport of transferred cells has provided new insights into the mechanisms of tumour immunotherapy. Recent studies have shown the effectiveness of cell-transfer therapies for the treatment of patients with selected metastatic cancers. These studies provide a blueprint for the wider application of adoptive-cell-transfer therapy, and emphasize the requirement for in vivo persistence of the cells for therapeutic efficacy.

摘要翻译： 

过继性免疫疗法——即分离抗原特异性细胞，在体外扩增与激活后回输自体——是诱导抗肿瘤免疫应答的一种前景广阔的策略。肿瘤抗原的分子鉴定以及追踪回输细胞在体内存续与迁移的能力，为阐明肿瘤免疫治疗机制提供了新洞见。近期研究已证实，细胞回输疗法对部分转移性癌症患者具有显著疗效，为更广泛应用过继性细胞回输疗法奠定了基础，并强调细胞在体内持久存在是疗效的关键。

原文链接：

Adoptive-cell-transfer therapy for the treatment of patients with cancer