Abstract B18: B-cell lymphoma patient-derived xenograft models: The road to personalized therapy

Lymphoma is the most common hematological malignancy, and B-cell lymphoma accounts for 85% of all lymphomas. The current overall cure rate for B-cell lymphoma is estimated at ~30%, even with the development and application of novel therapies, and the majority of patients relapse after treatment due to the development of drug resistance. The evaluation of novel drug targets using established B-cell lymphoma cell lines is limited by the inexact correlation between responsiveness observed in the cell line versus the patient sample. However, patient-derived xenograft (PDX) mouse models have been shown to recapitulate the diversity of growth, metastasis, and histopathology of the original tumor, overcoming the limitations of cell lines. Furthermore, recent studies have indicated that PDXs can recapitulate treatment responses of the parental tumor and can successfully choose a therapeutic target and regimen for the patient. We previously established a SCID-hu in vivo human primary mantle cell lymphoma (MCL) PDX model, the first human primary MCL animal model for biological and therapeutic research, and investigated the disease biology and potential novel human MCL therapies using this model. In this MCL PDX model, the engraftment and growth of patient MCL cells were dependent on the human bone marrow microenvironment supplied by an implanted human fetal bone chip. Our clinical information and reports show that numerous B-cell lymphoma subtypes involve bone marrow; therefore, we expanded our PDX model to include various B-cell lymphomas to study the clonal evolution of tumors and to evaluate novel therapies for the treatments of these diseases. PDX models (n=20) were established for multiple different types of B-cell lymphoma, including MCL (n=12), Burkitt9s lymphoma (n=1), marginal zone lymphoma (n=2), follicular lymphoma (n=2), chronic lymphocytic leukemia (n=1) and diffuse large B-cell lymphoma (n=2). The engraftment rate was high at 95%, the tumor xenografts rapidly grew at 3-4 weeks/generation, and 68% of the tumor xenografts were passaged for multiple generations, even up to 14 generations. Further demonstrating the utility of this model to recapitulate the characteristics of the original patient tumor, the tumor xenograft cells migrated to the lymph nodes, spleen, bone marrow, and gastrointestinal tract of the host mice, mimicking the disease progression observed in humans, and HE Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B18.