Abstract 1069: New panel of patient derived lymphoma xenografts (PDX) for preclinical research and immune oncology

Abstract

Abstract Lymphomas represent a very heterogeneous group of hematologic malignancies and pose an important challenge in the clinical routine. They frequently develop resistance to the treatment with standard-of-care (SoC) drugs and have a high incidence of disease recurrence. Recent progress in molecular high throughput profiling has helped to identify genetic drivers and genetic subtypes of diffuse large B-cell lymphomas (DLBCL). Further target validation and drug development projects are highly dependent on corresponding preclinical models representing the different clinical subtypes. Therefore, we started to establish and characterize new patient derived xenografts (PDX) of non-Hodgkin (NHL) and Hodgkin lymphomas (HL) for drug development, translational and immune oncology research. All lymphoma PDX were derived from peripheral blood, lymph node extirpations or core needle biopsies, and were usually transplanted subcutaneously into immunodeficient mice. For further characterization, established lymphoma PDX models were treated with SoC and investigational drugs. In addition, the growth of lymphoma PDX on humanized mice was evaluated to establish new models for the evaluation of novel immune therapy approaches. To gain a deeper insight in the molecular biology of the lymphoma models, RNA sequencing of all was performed. More than 20 new PDX models from NHL (including 8 DLBCL) and HL have been successfully established and characterized. Heterogeneous individual responses to the treatments were observed. Explorative analysis of RNA sequencing data confirmed the representation of the clinical lymphoma subgroups in our panel of models. Likewise, genetic subtypes of DLBCL COO classes could be confirmed by PCA and hierarchical clustering methods. Patterns of genetic driver mutations as revealed by recently published large genomic studies were identified. Our newly and extensively characterized lymphoma PDX model panel allows the evaluation on novel targeted and immune therapies in preclinical phase II trial settings. They provide an exceptional platform for the identification and validation of new targets and allow the preclinical screening of new combinations in translational research projects. Citation Format: Bernadette Brzezicha, Michael Becker, Maria Stecklum, Teresia Conrad, Martin Janz, Aitomi Bittner, Clemens Schmitt, Ulrich Keilholz, Jens Hoffmann. New panel of patient derived lymphoma xenografts (PDX) for preclinical research and immune oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1069.