Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish.

ABSTRACT: Xenograft cell transplantation into immunodeficient mice has become the gold standard for assessing pre-clinical efficacy of cancer drugs, yet direct visualization of single-cell phenotypes is difficult. Here, we report an optically-clear prkdc^-/-, il2rga^-/- zebrafish that lacks adaptive and natural killer immune cells, can engraft a wide array of human cancers at 37°C, and permits the dynamic visualization of single engrafted cells. For example, photoconversion cell-lineage tracing identified migratory and proliferative cell states in human rhabdomyosarcoma, a pediatric cancer of muscle. Additional experiments identified the preclinical efficacy of combination olaparib PARP inhibitor and temozolomide DNA-damaging agent as an effective therapy for rhabdomyosarcoma and

SUBMITTER: Yan C 

PROVIDER: S-EPMC6570580 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature