Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models

Ann Oncol. 2020 Feb;31(2):266-273. doi: 10.1016/j.annonc.2019.11.002. Epub 2020 Jan 3.


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.

Keywords: NOG mice; immunotherapy; melanoma; mouse models; patient-derived xenografts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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