Poster B59: Clinically Relevant DLBCL PDX Models for BTK Inhibitor Testing

Establishment of De Novo and Viral Induced B Lymphoma PDX Models to Evaluate Efficacy of the BTK Inhibitor Ibrutinib

Jessie Wang, Meiling Zheng, Chunjuan Huang, Xuesong Huang, Yanrui Song, Wubin Qian, Likun Zhang, Jie Cai, Sheng Guo, Henry Q. X. Li, Davy X. Ouyang

The activation of Bruton's tyrosine kinase (BTK) is considered as a major oncogenic driver for various B cell-derived lymphoid cancers. Ibrutinib (a BTK inhibitor), has been approved for a range of malignancies, and has also shown encouraging efficacy in the ABC subtype of DLBCL.

Clinically relevant DLBCL models are now needed for further preclinical testing of ibrutinib and other BTK inhibitors. To meet this need, CrownBio has established a series of patient-derived xenograft (PDX) models, recapitulating the diverse genotypes of de novo DLBCL patients including MYD88^L265P/CD79B^Y197N double mutants, a MYD88^L265P single mutant model, and a variety of wild type PDX.

To complement these models, we have also established a cohort of EBV-transformed B lymphoma PDX, which share the similar histopathology as de novo DLBCL, but have distinct molecular pathology signatures and different pathogenesis.

Read this Poster to Discover:

• The establishment and characterization of de novo and EBV-transformed B lymphoma PDX models, which show strikingly different pathogenesis and ibrutinib response
  
  
• That, in de novo DLBCL PDX models, CD79B activating mutation is a predictive biomarker for chronic activation of BCR signaling, and a generally good response to BTK inhibitors.
  
  
• That DLBCL and EBV-induced lymphoma PDX models provide a valuable preclinical platform for evaluating BTK inhibitors, as well as future drug discovery efforts on other targets in the BCR and MYD88 pathways, such as PI3K, SYK, and IRAK4

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