| Autor: |
Vivian Changying Jiang, Yang Liu, Alexa Jordan, Angela Leeming, Joseph McIntosh, Shengjian Huang, Rongjia Zhang, Qingsong Cai, Zhihong Chen, Yijing Li, Yuxuan Che, Lei Nie, Ingrid Karlsson, Linda Mårtensson, Mathilda Kovacek, Ingrid Teige, Björn Frendéus, Michael Wang |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Journal of hematologyoncology. 15(1) |
| ISSN: |
1756-8722 |
| Popis: |
Abstract Inevitable relapses remain as the major therapeutic challenge in patients with mantle cell lymphoma (MCL) despite FDA approval of multiple targeted therapies and immunotherapies. Fc gamma receptors (FcγRs) play important roles in regulating antibody-mediated immunity. FcγRIIB, the unique immune-checkpoint inhibitory member of the FcγR family, has been implicated in immune cell desensitization and tumor cell resistance to the anti-CD20 antibody rituximab and other antibody-mediated immunotherapies; however, little is known about its expression and its immune-modulatory function in patients with aggressive MCL, especially those with multi-resistance. In this study, we found that FcγRIIB was ubiquitously expressed in both MCL cell lines and primary patient samples. FcγRIIB expression is significantly higher in CAR T-relapsed patient samples (p p = 0.05) and rituximab-venetoclax (p = 0.02), but not the rituximab-CHOP combination in JeKo-1 cell line-derived xenograft models. In patient-derived xenograft (PDX) models, BI-1206, as a single agent, showed high potency (p R2 therapy). BI-1206 sensitized the efficacy of rituximab monotherapy in a PDX model with triple resistance to rituximab, ibrutinib and CAR T-therapies (p = 0.030). Moreover, BI-1206 significantly enhanced the efficacy of the rituximab-venetoclax combination (p Graphical Abstract |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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