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Blood, Dec 09 2024, blood.2024025673 | https://doi.org/10.1182/blood.2024025673
Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis
Seung Kwon Koh 1, Hyojin Kim 2, Bohwa Han 3, Hantae Jo 4, Junsang Doh 5, Jeehun Park Prof 6, Minh Ha Nguyen 7, Hyun-Young Kim 8, Haneul Kim 1, Seung-Hwan Lee 9, Chan Hyuk Kim 10, Duck Cho 8
1Department of Health Sciences and Technology, The Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea, Republic of.
2Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea, Republic of.
3Department of Materials Science and Engineering, Seoul National University, Seoul, Korea, Republic of.
4Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Seoul, Korea, Republic of.
5Seoul National University, Seoul, Korea, Republic of.
6Multidimensional Genomics Research Center, Kangwon National University, 1, Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, Republic of Korea, Korea, Republic of.
7Korea Advanced Institute of Science and Technology, Incheon, Korea, Republic of.
8Samsung Medical Center, Seoul, Korea, Republic of.
9Univesity of Ottawa, Ottawa, Canada.
10School of Transdisciplinary Innovations, Seoul National University, Seoul, Korea, Republic of.
*Corresponding Author: Duck Cho
1Department of Health Sciences and Technology, The Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea, Republic of.
2Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea, Republic of.
3Department of Materials Science and Engineering, Seoul National University, Seoul, Korea, Republic of.
4Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Seoul, Korea, Republic of.
5Seoul National University, Seoul, Korea, Republic of.
6Multidimensional Genomics Research Center, Kangwon National University, 1, Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, Republic of Korea, Korea, Republic of.
7Korea Advanced Institute of Science and Technology, Incheon, Korea, Republic of.
8Samsung Medical Center, Seoul, Korea, Republic of.
9Univesity of Ottawa, Ottawa, Canada.
10School of Transdisciplinary Innovations, Seoul National University, Seoul, Korea, Republic of.
*Corresponding Author: Duck Cho
Abstract
Anti-CD19 chimeric antigen receptor (CAR)-engineered T and NK cell therapies have revolutionized the treatment of B cell malignancies, but challenges including CD19 antigen loss greatly hinder their full therapeutic potential. Here we demonstrated that co-treatment with anti-CD19 monoclonal antibody enhances antitumor activity of anti-CD19 CAR-T and -NK cells. Even though the treated antibody interferes with CD19 antigen binding of CAR, it significantly induces rapid detachment of anti-CD19 CAR effector cells from target cells, facilitating improved serial killing. This reduced interaction between CAR effector cells and target cells also leads to the alleviation of CAR-mediated trogocytosis. Interestingly, co-treatment with anti-CD19 antibody reveals time-dependent effects on the antitumor activity of anti-CD19 CAR-T cells, characterized by a reduction in early T cell activation followed by sustained high activity during prolonged exposure to target cells. This temporal modulation ultimately results in enhanced antitumor potency in vivo. These findings underscore the improved therapeutic efficacy achieved by combining anti-CD19 antibody with anti-CD19 CAR-T or -NK cells against B cell malignancies.
논문정보
- Research article
- 2024년 12월 (BRIC 등록일 2024-12-10)
- 국내 연구진
- 의약학 > 면역의학
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