来自培养皿的采纳细胞疗法:诱导多能干细胞的潜能。

IF 1.9 4区 医学 Q3 HEMATOLOGY
Transfusion Medicine and Hemotherapy Pub Date : 2024-08-26 eCollection Date: 2025-02-01 DOI:10.1159/000540473
Pieter L Lindenbergh, Sjoukje J C van der Stegen
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引用次数: 0

摘要

背景:自体过继细胞疗法(ACT)的临床成功是实质性的,但广泛应用受到患者免疫细胞的质量和数量以及个性化制造工艺的需求的挑战。诱导多能干细胞(iPSCs)可以分化为免疫效应器,从而为ACT提供了另一种异体细胞来源。在这里,我们比较了ipsc衍生的免疫效应器和pbmc衍生的免疫效应器,并回顾了ipsc衍生的ACT产品目前正在临床前和临床开发中。ipsc衍生的T细胞、NK细胞、巨噬细胞和中性粒细胞在细胞表面标记物表达和细胞毒性效应功能方面很大程度上模仿pbmc衍生的细胞。ipsc衍生的免疫效应物可以与嵌合抗原受体和其他激活受体一起进行工程设计,以将其细胞毒性潜能特异性地转移到肿瘤相关抗原(TAAs)上。然而,iPSC衍生的免疫效应器和pbmc衍生的免疫效应器之间仍然存在一些差异,并激发了额外的工程策略来增强iPSC衍生的免疫效应器的抗肿瘤能力。关键信息:可以对iPSCs进行工程设计,以促进对TAAs具有均匀特异性的免疫效应物的产生,并增强效应物的功能。taa特异性和功能增强的ipsc衍生的T细胞和NK细胞目前正在进行临床1期试验评估。工程ipsc衍生的巨噬细胞和中性粒细胞正处于临床前开发阶段。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adoptive Cell Therapy from the Dish: Potentiating Induced Pluripotent Stem Cells.

Background: The clinical success of autologous adoptive cell therapy (ACT) is substantial but wide application is challenged by the quality and quantity of the patient's immune cells and the need for personalized manufacturing processes. Induced pluripotent stem cells (iPSCs) can be differentiated into immune effectors and thus provide an alternative, allogeneic cell source for ACT. Here, we compare iPSC-derived immune effectors to their PBMC-derived counterparts and review iPSC-derived ACT products currently under preclinical and clinical development.

Summary: iPSC-derived T cells, NK cells, macrophages, and neutrophils largely mimic their PBMC-derived counterparts in terms of cell-surface marker expression and cytotoxic effector functions. iPSC-derived immune effectors can be engineered with chimeric antigen receptors and other activating receptors to redirect their cytotoxic potential specifically to tumor-associated antigens (TAAs). However, several differences between iPSC- and PBMC-derived immune effectors remain and have inspired additional engineering strategies to enhance the antitumor capacity of iPSC-derived immune effectors.

Key messages: iPSCs can be engineered to facilitate the generation of immune effectors with homogenous specificity for TAAs and enhanced effector functions. TAA-specific and functionally enhanced iPSC-derived T and NK cells are currently undergoing clinical evaluation in phase 1 trials. Engineered iPSC-derived macrophages and neutrophils are in preclinical development.

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来源期刊
CiteScore
4.00
自引率
9.10%
发文量
47
审稿时长
6-12 weeks
期刊介绍: This journal is devoted to all areas of transfusion medicine. These include the quality and security of blood products, therapy with blood components and plasma derivatives, transfusion-related questions in transplantation, stem cell manipulation, therapeutic and diagnostic problems of homeostasis, immuno-hematological investigations, and legal aspects of the production of blood products as well as hemotherapy. Both comprehensive reviews and primary publications that detail the newest work in transfusion medicine and hemotherapy promote the international exchange of knowledge within these disciplines. Consistent with this goal, continuing clinical education is also specifically addressed.
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