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AACR 2023 Poster 4679

Molecular Pathology and BTKi Pharmacology of DLBCL PDX Models

Jingjing Wang1, Yueying Wang1, Wubin Qian1, Jia Xue1, Sheng Guo1, Likun Zhang1, Henry Li2

1Crown Bioscience, Inc., San Diego, California, USA
2Hanx Biopharmaceuticals Inc., Oceanside, California, USA

Diffuse large B cell lymphoma (DLBCL), the largest subtype of non-Hodgkin’s lymphoma (NHL), ~40%, is a heterogeneous disease with diverse pathogenesis. Epstein-Barr Virus positive DLBCL (EBV+ DLBCL) has also been recognized as a distinct subtype by WHO, originated from clonal B cell lymphoid proliferation, likely driven by EBV infection, which results in viral oncoprotein-induced transformations. BTK plays an exclusive and vital role in B cell development, and ibrutinib is a first-in class, orally-administered, selective and covalent BTK inhibitor (BTKi), approved for treating several B cell lymphomas, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but not yet for DLBCL. With the complexity of clinical trials, patient-derived xenografts (PDXs) become an alternative and powerful experimental system to investigate heterogeneous molecular pathology, and their corresponding pharmacology of DLBCLs.

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  • Creation of an unique PDX cohort representative of diverse subtypes of de novo DLBCL patients, along with 15 EBV transformed DLBCLs during xenografting

  • Molecular pathology analysis of the DLBCL PDX cohort

  • BTKi pharmacology response for EBV- and EBV+ DLBLC PDX

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