Improving the efficacy of osteosarcoma therapy: Combining drugs that turn cancer cell "don't eat me" signals off and "eat me" signals on. Molecular oncology Mohanty, S. n., Aghighi, M. n., Yerneni, K. n., Theruvath, J. L., Daldrup-Link, H. E. 2019

Abstract

The long-term survival of osteosarcoma patients with metastatic or recurrent disease remains dismal and new therapeutic options are urgently needed. The purpose of our study was to compare the efficacy of CD47 mAb plus doxorubicin combination therapy in mouse models of osteosarcoma with CD47 mAb and doxorubicin monotherapy. Forty-eight NOD scid gamma (NSG) mice with intratibial MNNG/HOS tumors received CD47 mAb, doxorubicin, combination therapy or control IgG treatment. Twenty-four mice (n=6 per group) underwent pre- and post-treatment MRI scans with the macrophage marker ferumoxytol, bioluminescence imaging and histological analysis. Tumor ferumoxytol enhancement, tumor flux and tumor TAM density were compared between different groups using a one-way ANOVA. Twenty-four additional NSG mice underwent survival analyses with Kaplan-Meier curves and a log-rank (Mantel-Cox) test. Intratibial osteosarcomas demonstrated significantly stronger ferumoxytol enhancement and significantly increased TAM quantities after CD47 mAb plus doxorubicin combination therapy compared to CD47 mAb (p = 0.02) and doxorubicin monotherapy (p = 0.001). Tumor bearing mice treated with CD47 mAb plus doxorubicin combination therapy demonstrated significantly reduced tumor size and prolonged survival compared to control groups that received CD47 mAb (p = 0.03), doxorubicin monotherapy (p = 0.01) and control IgG (p = 0.001). In conclusion CD47 mAb plus doxorubicin therapy demonstrates an additive therapeutic effect in mouse models of osteosarcomas, which can be monitored with an immediately clinically applicable MRI technique. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/1878-0261.12556

View details for PubMedID 31376208