Author Correction: A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

Candini, Olivia; Grisendi, Giulia; Foppiani, Elisabetta Manuela; Brogli, M.; Aramini, Beatrice; Masciale, Valentina; Spano, Carlotta; Petrachi, Tiziana; Veronesi, Elena; Conté, Pierfranco; Mari, Giorgio; Dominici, Massimo

doi:10.1038/s41598-020-57846-6

Cited by 8 publications

(5 citation statements)

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“…6a). To further address GD2 CAR T antitumor performance, we used a biocompatible 3D cell culture device that allows a rapid ex vivo rebuilding of the tumor's tissue-like structure 22 . Thus, C3 tumor cells were loaded and observed rapidly colonizing the 3D matrix and after 24 h either GD2 CAR T or control GFP T cells were added to the 3D culture at an E:T ratio of 5:1.…”

Section: Gd2 Car T Cytotoxic Activity Is Preserved In Two Distinct Th...mentioning

confidence: 99%

GD2 CAR T cells against human glioblastoma

et al. 2021

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Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment. We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines. Interestingly, immunosuppressant TGF β1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections. We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.

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Section: Gd2 Car T Cytotoxic Activity Is Preserved In Two Distinct Th...mentioning

confidence: 99%

GD2 CAR T cells against human glioblastoma

et al. 2021

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“…3D culture models allow researchers to recreate specific pathophysiological conditions and tumorigenic processes to identify potential biomarkers for therapeutic targeting or assessing cell response to therapies and drug efficacy. Currently, there has been significant interest in using primary clinical samples in 3D culture for personalised drug screening platforms to improve clinical outcomes and reduce side effects ( 178 , 179 ). Although there are still practical challenges in the widespread adoption of 3D cultures, advancements in this field will provide researchers with a powerful tool to dissect disease mechanisms, identify new biomarkers, provide valuable data in drug development, and realize the potential in the next generation of personalised medicine.…”

Section: Discussionmentioning

confidence: 99%

Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies

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Grundy³

et al. 2021

Front. Oncol.

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Over 90% of potential anti-cancer drug candidates results in translational failures in clinical trials. The main reason for this failure can be attributed to the non-accurate pre-clinical models that are being currently used for drug development and in personalised therapies. To ensure that the assessment of drug efficacy and their mechanism of action have clinical translatability, the complexity of the tumor microenvironment needs to be properly modelled. 3D culture models are emerging as a powerful research tool that recapitulates in vivo characteristics. Technological advancements in this field show promising application in improving drug discovery, pre-clinical validation, and precision medicine. In this review, we discuss the significance of the tumor microenvironment and its impact on therapy success, the current developments of 3D culture, and the opportunities that advancements that in vitro technologies can provide to improve cancer therapeutics.

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“…Significant advances over the past decades allow the application of 3D platforms suitable for studying cellular mechanisms and for identifying effective anticancer therapeutics under in vivo-like conditions [55,56]. For this reason, we used 3D organotypic cultures of pancreatic cancer cells and their derived CSCs growing on both a Matrigel-rich ECM or a collagen I-rich ECM that better recapitulate the transition of the native tumor and its surrounding microenvironment from its early development when the tumor cells are mainly exposed to the basal membrane, i.e., Matrigel, to the later stages of tumor progression, when the collagen-I predominates in the tumor ECM.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix Composition Modulates the Responsiveness of Differentiated and Stem Pancreatic Cancer Cells to Lipophilic Derivate of Gemcitabine

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Pozza

Greco

et al. 2020

IJMS

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Gemcitabine (GEM) is used as the gold standard drug in PDAC treatment. However, due to its poor efficacy, it remains urgent to identify novel strategies to overcome resistance issues. In this context, an intense stroma reaction and the presence of cancer stem cells (CSCs) have been shown to influence PDAC aggressiveness, metastatic potential, and chemoresistance. Methods: We used three-dimensional (3D) organotypic cultures grown on an extracellular matrix composed of Matrigel or collagen I to test the effect of the new potential therapeutic prodrug 4-(N)-stearoyl-GEM, called C18GEM. We analyzed C18GEM cytotoxic activity, intracellular uptake, apoptosis, necrosis, and autophagy induction in both Panc1 cell line (P) and their derived CSCs. Results: PDAC CSCs show higher sensitivity to C18GEM treatment when cultured in both two-dimensional (2D) and 3D conditions, especially on collagen I, in comparison to GEM. The intracellular uptake mechanisms of C18GEM are mainly due to membrane nucleoside transporters’ expression and fatty acid translocase CD36 in Panc1 P cells and to clathrin-mediated endocytosis and CD36 in Panc1 CSCs. Furthermore, C18GEM induces an increase in cell death compared to GEM in both cell lines grown on 2D and 3D cultures. Finally, C18GEM stimulated protective autophagy in Panc1 P and CSCs cultured on 3D conditions. Conclusion: We propose C18GEM together with autophagy inhibitors as a valid alternative therapeutic approach in PDAC treatment.

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Author Correction: A Novel 3D In Vitro Platform for Pre-Clinical Investigations in Drug Testing, Gene Therapy, and Immuno-oncology

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 8 publications

References 0 publications

GD2 CAR T cells against human glioblastoma

GD2 CAR T cells against human glioblastoma

Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies

Extracellular Matrix Composition Modulates the Responsiveness of Differentiated and Stem Pancreatic Cancer Cells to Lipophilic Derivate of Gemcitabine

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