| Literature DB >> 31138521 |
Yorleny Vicioso1, Hermann Gram2, Rose Beck1,3, Abhishek Asthana4, Keman Zhang4, Derek P Wong1, John Letterio5,6, Reshmi Parameswaran7,5.
Abstract
Drug-resistant acute lymphoblastic leukemia (ALL) patients do not respond to standard chemotherapy, and an urgent need exists to develop new treatment strategies. Our study exploited the presence of B-cell activating factor receptor (BAFF-R) on the surface of drug-resistant B-ALL cells as a therapeutic target. We used anti-BAFF-R (VAY736), optimized for natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC), to kill drug-resistant ALL cells. VAY736 antibody and NK cell treatments significantly decreased ALL disease burden and provided survival benefit in vivo However, if the disease was advanced, the ADCC efficacy of NK cells was inhibited by microenvironmental transforming growth factor-beta (TGFβ). Inhibiting TGFβ signaling in NK cells using the TGFβ receptor 1 (R1) inhibitor (EW-7197) significantly enhanced VAY736-induced NK cell-mediated ALL killing. Our results highlight the potential of using a combination of VAY736 antibody with EW-7197 to treat advance-stage, drug-resistant B-ALL patients. ©2019 American Association for Cancer Research.Entities:
Year: 2019 PMID： 31138521 PMCID： PMC6606383 DOI： 10.1158/2326-6066.CIR-19-0058
Source DB: PubMed Journal: Cancer Immunol Res ISSN： 2326-6066 Impact factor: 11.151