The Correlation Between Non-Hodgkin Lymphoma and Expression Levels of B-Cell Activating Factor and Its Receptors

Shen, Xianjuan; Wang, Mei; Guo, Yinglu; Ju, Shaoqing

doi:10.17219/acem/29182

Cited by 14 publications

(18 citation statements)

References 5 publications

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“…Following activation, BAFF-R regulates tumor survival and proliferation in an NF-κB-dependent manner (53,54). BAFF-R upregulation is associated with disease progression in patients with B-cell lymphoma and pre-B-ALL (55)(56)(57). The critical role of BAFF-R in B-cells positions it as an ideal target for adoptive immunotherapies (58-61).…”

Section: Strategies For Overcoming Antigen Escapementioning

confidence: 99%

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Kozani

O’Connor

2021

Molecular Cancer Therapeutics

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Combining synthetic biology with adoptive T-cell transfer has led to promising advances in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). Chimeric antigen receptors (CARs) are synthetic receptors that redirect T-cell specificity against cancer. CARs include “built-in” signaling domains that reprogram T-cell metabolism, enhance effector function, and support long-term persistence. Despite their success in blood-based malignancies, relapse can occur in CD19-redirected CAR T-cell therapies for several reasons, including poor engraftment, impaired in vivo proliferation, and T-cell senescence. Herein, we explain how subtle alterations in CAR design may overcome barriers to effective adoptive immunotherapy. We also discuss how the physiochemical properties of the single-chain variable fragment (scFv) affect differentiation and persistence. Moreover, we describe innovative advances in CAR engineering and provide insight into the development of humanized scFvs whose proposed benefits include increased persistence and improved clinical outcomes. Tumor cells can evade CAR T-cell–mediated detection and elimination due to the emergence or presence of CD19-negative leukemic cell subpopulations. We also discuss the opportunities and challenges in targeting other B-ALL–associated antigens. Identifying alternate targets is fundamentally necessary to restore the success of CAR T-cell therapies in CD19-negative patients with B-ALL.

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Section: Strategies For Overcoming Antigen Escapementioning

confidence: 99%

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

Kozani

O’Connor

2021

Molecular Cancer Therapeutics

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“…[10][11][12][13] Moreover, the serum level of BAFF was found to be elevated in patients with NHL, B-CLL, and MM cases. [14][15][16][17] The NHL patients with high BAFF serum levels showed an aggressive form of the disease and poor drug response. 18 The malignant B-cells and/or the cells present in the microenvironment are known to facilitate their growth and survival through altered BAFF production.…”

Section: Introductionmentioning

confidence: 99%

BAFF receptor antibody for mantle cell lymphoma therapy

et al. 2021

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Mantle cell lymphoma (MCL) is an aggressive form of B cell non-Hodgkin's lymphoma and remains incurable under current treatment modalities. One of the main reasons for treatment failure is the development of drug resistance. Accumulating evidence suggests that B cell activating factor (BAFF) and BAFF receptor (BAFF-R) play an important role in the proliferation and survival of malignant B cells. High serum BAFF levels are often correlated with poor drug response and relapse in MCL patients. Our study shows that BAFF-R is expressed on both MCL patient cells and cell lines. BAFF-R knockdown leads to MCL cell death showing the importance of BAFF-R signaling in MCL survival. Moderate knockdown of BAFF-R in MCL cells did not affect its viability, but sensitized them to cytarabine treatment in vitro and in vivo, with prolonged mice survival. Anti-BAFF-R antibody treatment promoted drug-induced MCL cell death. Conversely, the addition of recombinant BAFF (rhBAFF) to MCL cells protected them from cytarabine-induced apoptosis. We tested the efficacy of a humanized defucosylated ADCC optimized anti-BAFF-R antibody in killing MCL. Our data show both in vitro and in vivo efficacy of this antibody for MCL therapy. To conclude, our data indicate that BAFF/BAFF-R signaling is crucial for survival and involved in drug resistance of MCL. Targeting BAFF-R using BAFF-R antibody might be a promising therapeutical strategy to treat MCL patients resistant to chemotherapy.

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“…BCL10-related signaling controls the growth of cervical cancer cells via NF-κB-dependent cyclin D1 regulation [11]. Three BAFF receptors (BAFF-R, transmembrane activator and CAML interactor (TACI), and B-cell maturation antigen (BCMA)), which can specifically activate B lymphocytes and promote their proliferation, have been identified [12].…”

Section: Introductionmentioning

confidence: 99%

B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL/Lymphoma 10/Nuclear Factor-KappaB Signaling during Liver Regeneration

Chia-Hung

Lai

et al. 2019

IJMS

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B-cell activating factor (BAFF) is found to be associated with the histological severity of nonalcoholic steatohepatitis (NASH). BAFF was also found to have a protective role in hepatic steatosis via down regulating the expression of steatogenesis genes and enhancing steatosis in hepatocytes through BAFF-R. However, the roles of BAFF during liver regeneration are not well defined. In this study, C57/B6 mice with 70% partial hepatectomy were used as a liver regeneration model. BAFF expression was determined by enzyme immunoassay, and anti-BAFF-neutralizing antibodies were administered to confirm the effects of BAFF on liver regeneration. Western blotting, immunohistochemistry, and florescence staining determined the expression of B-cell CCL/lymphoma 10 (BCL10). The angiogenesis promoting capability was evaluated after the transfection of cells with siRNA targeting BCL10 expression, and the role of NF-κB was assessed. The results revealed that the BAFF and BCL10 levels were upregulated after partial hepatectomy. Treatment with anti-BAFF-neutralizing antibodies caused death in mice that were subjected to 70% partial hepatectomy within 72 h. In vitro, recombinant BAFF protein did not enhance hepatocyte proliferation; however, transfection with BCL10 siRNA arrested hepatocytes at the G2/M phase. Interestingly, conditioned medium from BAFF-treated hepatocytes enhanced angiogenesis and endothelial cell proliferation. Moreover, Matrix metalloproteinase-9 (MMP-9), Fibroblast growth factor 4 (FGF4), and Interleukin-8 (IL-8) proteins were upregulated by BAFF through BCL10/NF-κB signaling. In mice that were treated with anti-BAFF-neutralizing antibodies, the microvessel density (MVD) of the remaining liver tissues and liver regeneration were both reduced. Taken together, our study demonstrated that an increased expression of BAFF and activation of BCL10/NF-κB signaling were involved in hepatocyte-driven angiogenesis and survival during liver regeneration.

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The Correlation Between Non-Hodgkin Lymphoma and Expression Levels of B-Cell Activating Factor and Its Receptors

Cited by 14 publications

References 5 publications

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL

BAFF receptor antibody for mantle cell lymphoma therapy

B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL/Lymphoma 10/Nuclear Factor-KappaB Signaling during Liver Regeneration

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