이창한 (서울대학교 의과대학)

한빛사논문

조회92

서울대학교 의과대학

CV File 218 kb

Small Methods, Sep 11 2024, | https://doi.org/10.1002/smtd.202401016 Novel FRET-based Immunological Synapse Biosensor for the Prediction of Chimeric Antigen Receptor-T Cell Function

Hae Nim Lee ^1,2, Soojin Lee ^3,4,5, Jisu Hong ^1,3, Hyejin Yoo ⁶, Jiyun Jeong ¹, Yong-Woo Kim^3,4, Hyun Mu Shin ^2,3,4,5, Mihue Jang ^6,7, Chang-Han Lee ^1,2,3,4,5,8, Hang-Rae Kim ^2,3,4,5, Jihye Seong^1,2,3,4,8

¹Department of Pharmacology, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

²Medical Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

³Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

⁴Wide River Institute of Immunology, Seoul National University, Hongcheon, 25159, Republic of Korea.

⁵BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

⁶Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.

⁷Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea.

⁸Cancer Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea.

Corresponding Authors: Mihue Jang, Chang-Han Lee, Hang-Rae Kim, Jihye Seong

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. CARs are activated at the immunological synapse (IS) when their single-chain variable fragment (scFv) domain engages with an antigen, allowing them to directly eliminate cancer cells. Here, an innovative IS biosensor based on fluorescence resonance energy transfer (FRET) for the real-time assessment of CAR-IS architecture and signaling competence is presented. Using this biosensor, scFv variants for mesothelin-targeting CARs and identified as a novel scFv with enhanced CAR-T cell functionality despite its lower affinity than the original screened. The original CAR promoted internalization and trogocytosis, disrupting stable IS formation and impairing functionality are further observed. These findings emphasize the importance of enhancing IS quality rather than maximizing scFv affinity for superior CAR-T cell responses. Therefore, the FRET-based IS biosensor is a powerful tool for predicting CAR-T cell function, enabling the efficient engineering of next-generation CARs with enhanced antitumor potency.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-09-12)
연구진국내 연구진
분야 의약학 > 분자세포의학

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