Seimetz Diane, Heller Karl, Richter Jan
Biopharma Excellence GmbH, Munich, Germany.
Shire, Zug, Switzerland.
Cell Med. 2019 Jan 22;11:2155179018822781. doi: 10.1177/2155179018822781. eCollection 2019.
T cells are known as the most potent killer cells of the immune system, designed by nature to prevent unwanted challenges. The first class of therapeutic products harnessing the power of T cells for target-specific treatment of oncological diseases was bispecific antibodies. The first T-cell engaging bispecific antibodies that obtained approval were catumaxomab and blinatumomab. Eight years later, the first chimeric antigen receptor (CAR)-T cells received regulatory approval. CAR-T cells are the cellular interpretation of T-cell engaging therapies and have shown remarkable clinical results. CAR-T cells belong to the regulatory group of advanced therapy medicinal products (ATMPs). Due to the cell-/gene-based complex nature, ATMPs are far more challenging to develop than other, more defined, medicinal products. Despite very encouraging clinical results, there have been many set-backs in the development of ATMPs during the past 20 years. Therefore, the approval of the first two CAR-Ts KYMRIAH and YESCARTA is highly encouraging for the field. In this article we review the current landscape of CAR-Ts as a special class of ATMPs. This comprises the pathway to approval including the use of dedicated regulatory tools and challenges that were faced during the procedure. Furthermore, we highlight important future trends in the field.
T细胞被认为是免疫系统中最强大的杀伤细胞，是大自然为预防不良挑战而设计的。利用T细胞的力量针对肿瘤疾病进行靶向治疗的第一类治疗产品是双特异性抗体。首批获得批准的T细胞接合双特异性抗体是卡妥索单抗和博纳吐单抗。八年后，首个嵌合抗原受体（CAR）-T细胞获得监管批准。CAR-T细胞是T细胞接合疗法的细胞形式，并已显示出显著的临床效果。CAR-T细胞属于高级治疗药品（ATMP）的监管类别。由于基于细胞/基因的复杂性质，ATMP的开发比其他更明确的药品更具挑战性。尽管临床结果非常令人鼓舞，但在过去20年中，ATMP的开发仍遭遇了许多挫折。因此，首批两款CAR-T产品KYMRIAH和YESCARTA的获批对该领域极具鼓舞作用。在本文中，我们回顾了CAR-T作为一类特殊的ATMP的当前情况。这包括获批途径，包括专用监管工具的使用以及该过程中面临的挑战。此外，我们还强调了该领域未来的重要趋势。
