[논문]Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

Kim, Nayoung; Lee, Dong-Hee; Choi, Woo Seon; Yi, Eunbi; Kim, HyoJeong; Kim, Jung Min; Jin, Hyung-Seung; Kim, Hun Sik

doi:10.5483/bmbrep.2021.54.1.214

[국내논문] Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors 원문보기

BMB reports, v.54 no.1, 2021년, pp.44 - 58

Kim, Nayoung (Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) , Lee, Dong-Hee (Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) , Choi, Woo Seon (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) , Yi, Eunbi (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) , Kim, HyoJeong (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) , Kim, Jung Min (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine) , Jin, Hyung-Seung (Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) , Kim, Hun Sik (Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine)

Abstract ▼ AI-Helper

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

주제어

표/그림 (4)

그림 Fig. 1. Interactions between immune checkpoint receptors and their cognate ligands. NK cells express multiple immune checkpoint receptors, which can interact with their cognate ligands on tumor cells as well as other immune cells, in particular, dendritic cells and Tregs. The red circles represent immune checkpoint receptors while the blue circles represent the ligands. SIGLEC7 and SIGLEC9 have common ligands that are sialic acids. The pink squares represent the classical ITIM motif and the light blue squares represent the ITSM motif, which have been implicated in mediating inhibitory signals. The light green squares represent the ITT-like motif. Cytoplasmic domains of other immune checkpoint receptors contain fewer known motifs (not marked as squares). CD73 is a nucleotidase, which does not have conventional inhibitory signaling domains. The black lines indicate receptor-ligand interactions.
표 Table 1. Current status of clinical trials based on immune checkpoint receptors
그림 Fig. 2. Development of CAR-NK cell therapies in the industry. (A) GoCAR-NK utilizes Rimiducid and Rapamycin for inducible activation and suicide signaling, respectively. (B) FT596, combined with Rituximab, can target both CD19 and CD20 with CD16 Fc receptor in B cell malignancy. IL-15 receptor fusion protein with a flexible IL-15 is introduced for further NK cell activation. (C) ONK therapeutics use TRAIL signaling for maximizing tumor cell apoptosis. A high-affinity variant of TRAIL is recognized by the DR5 TRAIL receptor, thereby resulting in activation of FADDCaspase8 signaling in a target tumor cell. (D) t-haNK is a versatile platform targeting tumors with a combination of CAR and therapeutic antibody. In this figure, we illustrate an example of NSCLC which expresses a high level of PD-L1 and EGFR. ER-retained IL-2 also drives NK cell activation and persistence. (E) NKX-101 uses NKG2D-CAR for tumor antigen recognition, membrane-bound IL- 15 for further activation as well. NKG2D ligands (MIC and RAET1 families) are highly expressed in various tumor cells.
표 Table 2. Clinical trials with CAR-NK cells

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표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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