Establishment of Patient-Derived Xenotransplant and Cell Line Models for Canine B-Cell Lymphoma

Abstract

High-grade canine B-cell lymphoma (cBCL) is a spontaneous cancer in dogs with similar pathologic features as human diffuse large B-cell lymphoma (DLBCL). The value of comparative oncology to both dogs and humans has long been recognized, but the progress in cBCL research has been hampered by a scarcity of preclinical models. This study aimed to establish and characterize novel patient-derived xenograft (PDX) and cell line models from primary cBCL tumors to address this critical gap. To this end, primary cBCL tumors from three canine patients were surgically excised and serially transplanted into immunodeficient NOD scid gamma (NSG) mice. The resulting PDX models were characterized across passages in mice using histology, flow cytometry, single-nucleotide polymorphism (SNP) genotyping, and RNA sequencing. The results show that the samples retain many of their original characteristics, even after multiple NSG passages. Cancer cells from two of the PDX lines were successfully adapted to in vitro culture, creating two new established cell lines which were then used in drug sensitivity assays. The successful generation and characterization of these cBCL PDX and cell lines provides a valuable resource for canine cancer research and associated comparative oncology approaches.