التفاصيل البيبلوغرافية
| العنوان: |
Clinical activity of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, in refractory adult T-Cell leukemia/lymphoma. |
| المؤلفون: |
Hsu, Andrew1 (AUTHOR), Huntington, Kelsey E.2,3 (AUTHOR), De Souza, Andre1,2 (AUTHOR), Zhou, Lanlan2,3 (AUTHOR), Olszewski, Adam J.1,2 (AUTHOR), Makwana, Nirav P.4 (AUTHOR), Treaba, Diana O.3 (AUTHOR), Cavalcante, Ludimila5 (AUTHOR), Giles, Francis J.5 (AUTHOR), Safran, Howard1,2 (AUTHOR), El-Deiry, Wafik S.1,2,3 (AUTHOR), Carneiro, Benedito A.1,2 (AUTHOR) benedito_carneiro@brown.edu |
| المصدر: |
Cancer Biology & Therapy. 2022, Vol. 23 Issue 1, p417-423. 7p. |
| مصطلحات موضوعية: |
*GLYCOGEN synthase kinase-3, *ADULT T-cell leukemia, *SMALL molecules, *GRANZYMES, *LYMPHADENITIS, *KILLER cells, *CELL populations |
| مستخلص: |
GSK-3β is a serine/threonine kinase implicated in tumorigenesis and chemotherapy resistance. GSK-3β blockade downregulates the NF-κB pathway, modulates immune cell PD-1 and tumor cell PD-L1 expression, and increases CD8 + T cell and NK cell function. We report a case of adult T-cell leukemia/lymphoma (ATLL) treated with 9-ING-41, a selective GSK-3β inhibitor in clinical development, who achieved a durable response. A 43-year-old male developed diffuse lymphadenopathy, and biopsy of axillary lymph node showed acute-type ATLL. Peripheral blood flow cytometry revealed a circulating clonal T cell population, and CSF was positive for ATLL involvement. After disease progression on the 3rd line of treatment, he started treatment with 9-ING-41 monotherapy in a clinical trial (NCT03678883). CT imaging after seven months showed a partial response. Sustained reduction of peripheral blood ATLL cells lasted 15 months. Treatment of patient-derived CD8 + T cells with 9-ING-41 increased the secretion of IFN-γ, granzyme B, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In conclusion, treatment of a patient with refractory ATLL with the GSK-3β inhibitor 9-ING-41 resulted in a prolonged response. Ongoing experiments are investigating the hypothesis that 9-ING-41-induced T cell activation and immunomodulation contributes to its clinical activity. Further clinical investigation of 9-ING-41 for treatment of ATLL is warranted. [ABSTRACT FROM AUTHOR] |
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