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Fig. 5 In vivo autologous self-targeting efficacy of DR-KO tumor cells co-engineered with a secretable DRL and a suicide system. In vivo autologous self-targeting.

Published byΜατθαίος Κόρακας Modified over 5 years ago

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Presentation on theme: "Fig. 5 In vivo autologous self-targeting efficacy of DR-KO tumor cells co-engineered with a secretable DRL and a suicide system. In vivo autologous self-targeting."— Presentation transcript:

1 Fig. 5 In vivo autologous self-targeting efficacy of DR-KO tumor cells co-engineered with a secretable DRL and a suicide system. In vivo autologous self-targeting efficacy of DR-KO tumor cells co-engineered with a secretable DRL and a suicide system. (A) Photomicrograph time course of sECM-encapsulated ST-secreting rGBMnDR4/5-ST-TK cocultured with their autologous DR wild-type parental cells (sGBMnRec-FmC). Scale bar, 200 μm. (B) rGBMnDR4/5-ST-TK was engineered with GFl. The graph on the left shows in vitro correlation of Fluc signal with cell number. rGBMnDR4/5-ST-TK-GFl was encapsulated in sECM, followed by intracranial implantation into SCID mice. The graph on the right shows Fluc signal of rGBMnDR4/5-ST-TK-GFl before and after GCV treatment (n = 2 mice). (C) Top: Experimental outline for testing efficacy of sECM-encapsulated rGBMnDR4/5-ST-TK in mice with resected sGBMnRec-FmC tumors. Photomicrographs show light and fluorescence photos of intact and resected intracranial tumors after implantation of therapeutic cells. Scale bars, 1 mm. Black/white dashed circles indicate tumor area. The bar graph on the right shows mean tumor volume estimated on the basis of Fluc signal before and after resection (n = 28). Middle: Estimate of relative tumor volume after resection in treatment groups based on Fluc signal intensity of sGBMnRec-FmC-bearing mice (left). Kaplan-Meier survival curves are shown on the right (control, n = 4; resection alone, n = 4; rGBMnDR4/5-ST-TK -GCV, n = 11; rGBMnDR4/5-ST-TK + GCV, n = 13). Bottom: Representative hematoxylin and eosin (H&E)–stained sections and immunofluorescence photomicrographs of nonresected control versus resected sGBMnRec-FmC tumors treated with therapeutic rGBMnDR4/5-ST-TK with or without GCV. Scale bars, 200 μm. (D) Top: Experimental outline for testing the efficacy of rGBMiDR4/5 (control) or rGBMiDR4/5-ST-TK in mice bearing intracranial sGBMiRec-FmC tumors. Middle: Estimate of relative tumor volume in treatment groups based on Fluc signal of sGBMiRec-FmC–bearing mice (left) and respective Kaplan-Meier survival curves (right) (rGBMiDR4/5, n = 7; rGBMiDR4/5-ST-TK − GCV, n = 9, rGBMiDR4/5-ST-TK + GCV, n = 8). Bottom: Immunofluorescence photomicrograph of sGBMiRec-FmC–bearing mice injected with rGBMiDR4/5-ST-TK (no GCV treatment). Scale bar, 200 μm. (E) Top: Experimental outline for testing efficacy of rBCmDR4/5-ST-TK injected via the internal carotid artery (ICA) in mice bearing intracranial sBCm-RmC tumors. Bottom: Estimate of relative tumor volume increase based on Rl signal intensity of sBCm-RmC–bearing mice (left) and respective Kaplan-Meier survival curves (right) (PBS, n = 3; rBCmDR4/5-ST-TK − GCV, n = 3; rBCmDR4/5-ST-TK + CGV, n = 4). Means ± SEM are shown. P values by unpaired t test (C, top) or Mantel-Cox (log-rank) test (survival curves), *P < 0.05, **P < 0.01, ****P < Clemens Reinshagen et al., Sci Transl Med 2018;10:eaao3240 Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

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