Jessie J Wang, Meiling Zheng, Chunjuan Huang, Xuesong Huang, Yanrui Song, Wubin Qian, Likun Zhang, Jie Cai, Sheng Guo, Henry Q. X. Li, Davy X. Ouyang
Bruton's tyrosine kinase (BTK) activation is a major oncogenic driver for various B cell-derived lymphoid cancers. The BTK inhibitor ibrutinib has been approved for a range of malignancies (e.g. mantle cell lymphoma, chronic lymphocytic leukemia), and has also shown encouraging efficacy in the ABC subtype, but not GCB subtype, of DLBCL.
To allow further testing of ibrutinib in vivo for DLBCL, clinically relevant preclinical models are needed which recapitulate the diverse genotypes of de novo DLBCL patients, covering the different subtypes and single/double gene mutations. CrownBio has therefore established a series of patient-derived xenograft (PDX) DLBCL models, including wild type PDX, the MYD88L265P single mutant model, and two MYD88L265P/CD79BY197N double mutant PDX.
These models have been tested with ibrutinib (with continuous administration of a low dose through drinking water trialed), alongside a cohort of EBV-transformed B lymphoma PDX, which share similar histopathology with de novo DLBCL, but have distinct molecular pathology signatures and different pathogenesis.