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

L Ny, L Y Rizzo, V Belgrano, J Karlsson, H Jespersen, L Carstam, R O Bagge, L M Nilsson, J A Nilsson

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)266-273
Number of pages8
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Volume31
Issue number2
DOIs
Publication statusPublished - Feb 2020
Externally publishedYes

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