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Ann Oncol ; 31(2): 266-273, 2020 02.
Article in English | MEDLINE | ID: mdl-31959343

ABSTRACT

BACKGROUND: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. PATIENTS AND METHODS: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. RESULTS: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. CONCLUSIONS: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.


Subject(s)
Melanoma , Animals , Clinical Decision-Making , Heterografts , Humans , Melanoma/drug therapy , Melanoma/genetics , Mice , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Prospective Studies , Retrospective Studies , Xenograft Model Antitumor Assays
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