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. 2020 Feb;26(2):130-137.
doi: 10.1177/1753425919876690. Epub 2019 Sep 23.

Irradiation or temozolomide chemotherapy enhances anti-CD47 treatment of glioblastoma

Sharareh Gholamin  1   2 , Osama A Youssef  3 , Marjan Rafat  4 , Rogelio Esparza  1 , Suzana Kahn  1   2 , Maryam Shahin  4 , Amato J Giaccia  4 , Edward E Graves  4 , Irving Weissman  2 , Siddhartha Mitra  1   2   5 , Samuel H Cheshier  1   2   3
Affiliations

V体育安卓版 - Irradiation or temozolomide chemotherapy enhances anti-CD47 treatment of glioblastoma

Sharareh Gholamin et al. Innate Immun. 2020 Feb.

Abstract

Irradiation and temozolomide (TMZ) chemotherapy are the current standard treatments for glioblastoma multiforme (GBM), but they are associated with toxicity and limited efficacy VSports手机版. Recently, these standard therapies have been used to enhance immunotherapy against GBM. Immunotherapy using the anti-CD47 (immune checkpoint inhibitor) treatment has shown promise in treating multiple tumor types, including GBM. The goal of this current work was to test whether irradiation or TMZ chemotherapy could enhance anti-CD47 treatment against GBM. Our results showed that irradiation and TMZ each significantly enhanced anti-CD47-mediated phagocytosis of GBM cells in vitro. Furthermore, mice engrafted with human GBM that received anti-CD47 combined with focal irradiation or TMZ treatment showed a significant increase in the survival rate compared to those that received a single treatment. The tumor growth in mice that received both anti-CD47 and irradiation was significantly less than that of groups that received either anti-CD47 or focal irradiation. The results from this study may support future use of anti-CD47 treatment in combination with irradiation or chemotherapy to enhance the therapeutic efficacy of GBM treatment. .

Keywords: Glioblastoma; anti-CD47; irradiation; macrophages; phagocytosis; temozolomide V体育安卓版. .

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Figures

Figure 1.
Figure 1.
Effect of combining anti-CD47 treatment with irradiation or TMZ chemotherapy on the macrophage-dependent phagocytosis of glioblastoma multiforme (GBM) in vitro. (a) GBM tumor cells were treated with Hu5F9-G4 (Hu5F9), 2 or 8 Gy irradiation (IR), or both and subjected to phagocytosis by PBMC-derived macrophages. (b) GBM tumor cells were treated with Hu5F9-G4 (Hu5F9), 0, 25, 100, and 500 µM TMZ, or both and subjected to phagocytosis by PBMC-derived macrophages. Control=non-binding IgG4 alone, and DMSO at the same concentration the TMZ was diluted in. Data were normalized against anti-CD47 treatment alone.
Figure 2.
Figure 2.
Effect of combining anti-CD47 with irradiation on GBM-bearing mice. (a) Bioluminescence measurements (photons/sec) of GBM and (b) survival rate analysis of PDX mice treated with Hu5F9-G4 (Hu5F9), 10 Gy IR, or both. ****P < 0.0001; ***P < 0.0002.
Figure 3.
Figure 3.
Effect of combining anti-CD47 with TMZ chemotherapy on GBM-bearing mice. Survival rate analysis of PDX mice treated with Hu5F9-G4 (Hu5F9), TMZ, or both. ****P < 0.0001.
Figure 4.
Figure 4.
Model of macrophage-dependent phagocytosis after treating GBM cells with anti-CD47, irradiation, TMZ, or a combination of anti-CD47 with irradiation or TMZ. The model shows an enhancement in the macrophage engulfment of GBM cells after combining irradiation or TMZ with anti-CD47 treatment (bar at bottom) via treatment induced increase of pro-phagocytic signals on tumor cells.
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