Trial Watch: Adoptive cell transfer immunotherapy.
Trial Watch: Adoptive cell transfer immunotherapy.
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DOI：
10.4161/onci.19549
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发表时间：
2012-05-01
期刊：
影响因子：
7.2
通讯作者：
Kroemer G
中科院分区：
文献类型：
--
作者：
Galluzzi L;Vacchelli E;Eggermont A;Fridman WH;Galon J;Sautès-Fridman C;Tartour E;Zitvogel L;Kroemer G
在过去的二十年中，已经开发了几种激活免疫系统对抗癌症的方法。这些包括相当非选择性的操作，例如全身施用免疫刺激剂（例如，白细胞介素-2）以及靶向干预措施，包括高度特异性的单克隆抗体、疫苗和基于细胞的疗法。在后者中，过继性细胞转移（ACT）涉及选择具有抗肿瘤活性的自体淋巴细胞，其离体扩增/活化，以及其回输到患者体内，通常在淋巴细胞清除方案的背景下（以最小化内源性免疫抑制）。这样的自体细胞可以从肿瘤浸润淋巴细胞中分离或通过操纵循环淋巴细胞以表达肿瘤特异性T细胞受体来产生。此外，自体淋巴细胞可以被遗传工程化以延长其体内持久性，以增强抗肿瘤应答和/或使副作用最小化。ACT最近被证明与黑色素瘤和肾细胞癌患者的持久消退率一致相关，并在其他几种肿瘤学环境中具有很大的前景。在本试验观察中，我们将简要回顾ACT背后的科学原理，并讨论最近评估过继细胞转移作为抗癌疗法的安全性和有效性的临床试验的进展。
During the last two decades, several approaches for the activation of the immune system against cancer have been developed. These include rather unselective maneuvers such as the systemic administration of immunostimulatory agents (e.g., interleukin-2) as well as targeted interventions, encompassing highly specific monoclonal antibodies, vaccines and cell-based therapies. Among the latter, adoptive cell transfer (ACT) involves the selection of autologous lymphocytes with antitumor activity, their expansion/activation ex vivo, and their reinfusion into the patient, often in the context of lymphodepleting regimens (to minimize endogenous immunosuppression). Such autologous cells can be isolated from tumor-infiltrating lymphocytes or generated by manipulating circulating lymphocytes for the expression of tumor-specific T-cell receptors. In addition, autologous lymphocytes can be genetically engineered to prolong their in vivo persistence, to boost antitumor responses and/or to minimize side effects. ACT has recently been shown to be associated with a consistent rate of durable regressions in melanoma and renal cell carcinoma patients and holds great promises in several other oncological settings. In this Trial Watch, we will briefly review the scientific rationale behind ACT and discuss the progress of recent clinical trials evaluating the safety and effectiveness of adoptive cell transfer as an anticancer therapy.