دورية أكاديمية
KLRG1 cell depletion as a novel therapeutic strategy in patients with mature T-cell lymphoma subtypes
| العنوان: | KLRG1 cell depletion as a novel therapeutic strategy in patients with mature T-cell lymphoma subtypes |
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| المؤلفون: | Assatova, Bimarzhan, Willim, Robert, Trevisani, Christopher, Haskett, Garrett, Kariya, Khyati Maulik, Chopra, Kusha, Park, Sung Rye, Tolstorukov, Michael Yevgeniy, McCabe, Sean M., Duffy, Jessica, Louissaint, Abner, Huuhtanen, Jani, Bhattacharya, Dipabarna, Mustjoki, Satu, Koh, Min Jung, Powers, Foster, Morgan, Elizabeth A., Yang, Lei, Pinckney, Brandy, Cotton, Matthew J., Crabbe, Andrew, Ziemba, Jessica Beth, Brain, Ian, Heavican-Foral, Tayla B., Iqbal, Javeed, Nemec, Ronald, Rider, Anna Baird, Ford, Josie Germain, Koh, Min Ji, Scanlan, Nora, Feith, David J., Loughran, Thomas P., Kim, Won Seog, Choi, Jaehyuk, Roels, Juliette, Böhme, Lena, Putteman, Tom, Taghon, Tom, Barnes, Jeffrey A., Johnson, P. Connor, Jacobsen, Eric D., Greenberg, Steven A., Weinstock, David M., Jain, Salvia |
| المصدر: | CLINICAL CANCER RESEARCH ; ISSN: 1078-0432 ; ISSN: 1557-3265 |
| سنة النشر: | 2024 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, Biology and Life Sciences, Cancer Research, Oncology |
| الوصف: | Purpose: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms. Experimental Design: Primary specimens, cell lines, patient-derived xenograft models, commercially available, and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation. Results: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL), and gamma/delta T-cell lymphoma (G/D TCL). The majority of the CD8+/CD57+ or CD3−/CD56+ leukemic cells derived from patients with T- and NK-large granular lymphocytic leukemia (T-LGLL and NK-LGLL), respectively, expressed surface KLRG1. The humanized afucosylated anti-KLRG1 monoclonal antibody (mAb208) optimized for mouse in vivo use depleted KLRG1+ TCL cells by mechanisms of ADCC, ADCP, and CDC rather than apoptosis. mAb208 induced ADCC and ADCP of T-LGLL patient-derived CD8+/CD57+ cells ex vivo. mAb208 effected ADCC of subsets of healthy donor-derived KLRG1+ NK, CD4+, CD8+ Tem, and TemRA cells while sparing KLRG1− naïve and CD8+ Tcm cells. Treatment of cell line and TCL patient-derived xenografts with mAb208 or anti-CD47 mAb alone and in combination with the PI3K-δ/γ inhibitor duvelisib extended survival. The depletion of macrophages in vivo antagonized mAb208 efficacy. Conclusions: Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/01HSK6ZB06NGPC6QT80T1GTAY6Test; http://hdl.handle.net/1854/LU-01HSK6ZB06NGPC6QT80T1GTAY6Test; http://doi.org/10.1158/1078-0432.ccr-23-3504Test; https://biblio.ugent.be/publication/01HSK6ZB06NGPC6QT80T1GTAY6/file/01HTMQMG5E2QR3498QTG384Q5WTest |
| DOI: | 10.1158/1078-0432.ccr-23-3504 |
| الإتاحة: | https://doi.org/10.1158/1078-0432.ccr-23-3504Test https://biblio.ugent.be/publication/01HSK6ZB06NGPC6QT80T1GTAY6Test http://hdl.handle.net/1854/LU-01HSK6ZB06NGPC6QT80T1GTAY6Test https://biblio.ugent.be/publication/01HSK6ZB06NGPC6QT80T1GTAY6/file/01HTMQMG5E2QR3498QTG384Q5WTest |
| حقوق: | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1D872210 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/1078-0432.ccr-23-3504 |
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