VIVA-University Children's Cancer Centre, Khoo-Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore.
Department of Paediatrics, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.
Front Immunol. 2023 Jan 11;13:1044946. doi: 10.3389/fimmu.2022.1044946. eCollection 2022.
The ideal strategy to fight an infection involves both (i) weakening the invading pathogen through conventional antimicrobial therapy, and (ii) strengthening defense through the augmentation of host immunity. This is even more pertinent in the context of invasive fungal infections whereby the majority of patients have altered immunity and are unable to mount an appropriate host response against the pathogen. Natural killer (NK) cells fit the requirement of an efficient, innate executioner of both tumour cells and pathogens - their unique, targeted cell killing mechanism, combined with other arms of the immune system, make them potent effectors. These characteristics, together with their ready availability (given the various sources of extrinsic NK cells available for harvesting), make NK cells an attractive choice as adoptive cellular therapy against fungi in invasive infections. Improved techniques in NK cell activation with expansion, and more importantly, recent advances in genetic engineering including state-of-the-art chimeric antigen receptor platform development, have presented an opportune moment to harness this novel therapeutic as a key component of a multipronged strategy against invasive fungal infections.
对抗感染的理想策略包括(i) 通过常规的抗菌治疗削弱入侵病原体，以及(ii) 通过增强宿主免疫力来加强防御。在侵袭性真菌感染的情况下，这一点更为重要，因为大多数患者的免疫功能发生改变，无法对病原体产生适当的宿主反应。自然杀伤 (NK) 细胞符合作为肿瘤细胞和病原体的有效、先天执行者的要求-它们独特的、靶向性的细胞杀伤机制，结合免疫系统的其他部分，使它们成为有效的效应物。这些特性，加上它们的易得性（鉴于可用于采集的各种外源性 NK 细胞来源），使 NK 细胞成为治疗侵袭性感染中真菌的过继细胞治疗的一个有吸引力的选择。NK 细胞激活和扩增的技术得到了改进，更重要的是，基因工程的最新进展，包括最先进的嵌合抗原受体平台的开发，为利用这种新型治疗方法作为侵袭性真菌感染多管齐下策略的关键组成部分提供了一个契机。
