Abstract 3005: Establishment and characterization of a series of lymphoma PDX models representing varied clinical behaviors and treatment responses

Abstract

Abstract Background: Lymphomas are comprised of a heterogeneous group of hematologic malignancies based on different origins with diverse patterns of clinical behavior and treatment response. Pathologically, lymphomas are divided into two main subtypes, Hodgkin (HL) and non-Hodgkin (NHL), which account for around 10% and 90% of cases, respectively. NHL is further divided into B cell, T cell and natural killer (NK) cell subtypes. Besides histopathology, cancer is increasingly recognized as a genetic disease with specific molecular alterations, such as ALK translocation in anaplastic large cell lymphoma, MYC/BCL2/BCL6 translocation in B cell lymphoma (often referred to as ‘double-hit' or ‘triple-hit') and other specific mutations or overexpression. Current clinical therapeutic options for lymphoma therefore need to consider not only the histological type, clinical aggressiveness and cancer stage, but also the molecular markers, cytokine signaling, epigenetic aberrations and lymphoma microenvironment. Preclinical modeling with diverse types of lymphomas and deep characterization are important for the drug discovery of new lymphoma treatments. Methods: We have established and characterized a number of different subtypes of lymphoma patient-derived xenograft (PDX) models including both mature T/NK cell neoplasms and B cell neoplasms. Immunodeficient mice were used for establishment of these lymphoma PDX models with subcutaneous or tail vein engraftment. Model classification and characterization were determined by histopathology and IHC, as well as genomic profiling by next-generation sequencing (NGS) and response to chemo- or targeted therapies. Results: We have developed and characterized a large panel of lymphoma PDX models with various subtypes, including mantle cell lymphoma, angioimmunoblastic T cell lymphoma, ALK negative anaplastic large cell lymphoma, adult T cell leukemia/lymphoma, peripheral T cell lymphoma, extranodal NK/T cell lymphoma and also other common B cell lymphomas such as DLBCL and follicular lymphoma. Histopathology analysis of these models is in line with clinical pathology diagnosis. Additionally, cancer type-specific biomarkers, such as CD3, CD20, BCL2, BCL6 and MYC, were used for characterization of these lymphoma models by IHC. The response to subtype-specific chemotherapy or targeted therapies, such as CHOP, BTK inhibitors, CD38 antibodies etc., are now tested in some of these lymphoma PDX models and will be presented at the meeting. Conclusions: Lymphomas have diverse subtypes, represented by different clinical features and treatment responses. We have established and characterized a series of lymphomas with varied types including a large cohort of B cell lymphoma and T/NK cell lymphoma PDX models for drug evaluation. Citation Format: Jessie J. Wang, Yanrui Song, Jitai Zheng, Guiqing Wu, Likun Zhang, Henry Q.X. Li, Davy Xuesong Ouyang. Establishment and characterization of a series of lymphoma PDX models representing varied clinical behaviors and treatment responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3005.