ABSTRACT

Introduction

Adoptive immunotherapy of cancer has evolved from the use of ex vivo expanded lymphokine-activated killer cells and tumor-infiltrating lymphocytes to an increasing array of approaches involving genetically engineered T-cells. A pivotal advance in the enablement of these therapies has been the conditioning of patients with lymphodepleting chemotherapy.

A broad range of lymphodepleting regimens has been employed in an effort to improve response rates, without any single consistent approach having emerged. Only a limited number of studies involving small numbers of patients has directly compared two or more regimens, making it challenging to infer which are the preferred agents and dosing schedules. This difficulty is compounded by the fact that both response rate and toxicity appear to be disease-, patient- and T-cell product specific.

Expert Opinion

This article surveys clinical experience with lymphodepleting regimens that have been used in conjunction with adoptive T-cell immunotherapy, focussing in particular on studies where different approaches have been employed. Harnessing this limited and evolving clinical experience, we set out to provide potential insights into how an optimal balance may be achieved between efficacy and safety. Intermediate dose fludarabine-based regimens are emerging as an increasingly popular option in an attempt to achieve this goal, although further studies are required to provide definitive evidence.

中文翻译：

---

增强过继性 T 细胞免疫疗法的淋巴去除策略——我们在做什么；我们去哪？

摘要

介绍

癌症的过继免疫疗法已经从使用体外扩增的淋巴因子激活杀伤细胞和肿瘤浸润淋巴细胞发展为越来越多的涉及基因工程 T 细胞的方法。启用这些疗法的一个关键进展是对接受淋巴耗竭化疗的患者进行调理。

为了提高反应率，已经采用了广泛的淋巴清除方案，但没有出现任何单一的一致方法。只有少数涉及少量患者的研究直接比较了两种或多种方案，因此很难推断出哪些是首选药物和给药方案。由于反应率和毒性似乎是特定于疾病、患者和 T 细胞产品的事实，这一困难更加复杂。

专家意见

本文调查了与过继 T 细胞免疫疗法结合使用的淋巴清除方案的临床经验，特别关注采用不同方法的研究。利用这种有限且不断发展的临床经验，我们着手提供有关如何在疗效和安全性之间实现最佳平衡的潜在见解。为了实现这一目标，中剂量氟达拉滨方案正在成为一种越来越受欢迎的选择，尽管需要进一步的研究来提供明确的证据。