Ex vivo lung cancer spheroids resemble treatment response of a patient with NSCLC to chemotherapy and immunotherapy: case report and translational study

Liello, Raimondo Di; Ciaramella, Vincenza; Barra, Giusi; Venditti, Massimo; Corte, Carminia Maria Della; Papaccio, Federica; Sparano, Francesca; Viscardi, Giuseppe; Iacovino, Maria Lucia; Minucci, Sergio; Fasano, Morena; Ciardiello, Fortunato; Morgillo, Floriana

doi:10.1136/esmoopen-2019-000536

Cited by 32 publications

(24 citation statements)

References 18 publications

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“…Lagies et al found that 3D spheroid cultures shared strikingly metabolic similarities to the organ tissue such that authors suggested optimised 3D culture techniques could possibly replace animal testing [ 51 ]. Furthermore, Di Liello et al cultured 3D spheroids from patient derived non-small cell lung cancer tumours for ex-vivo analysis [ 52 ]. Authors reported that drug sensitivities to cisplatin-based chemotherapy and anti-programmed death 1 drug sensitivity were consistent from the patient clinical response to 3D culture.…”

Section: Discussionmentioning

confidence: 99%

Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme

et al. 2021

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Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types including GBM. In this study, a nano-formulation with the RALA peptide was used to complex the N-BP, alendronate (ALN) into nanoparticles (NPs) < 200 nm for optimal endocytic uptake. Fluorescently labelled AlexaFluor®647 Risedronate was used as a fluorescent analogue to visualise the intracellular delivery of N-BPs in both LN229 and T98G GBM cells. RALA NPs were effectively taken up by GBM where a dose-dependent response was evidenced with potentiation factors of 14.96 and 13.4 relative to ALN alone after 72 h in LN229 and T98G cells, respectively. Furthermore, RALA/ALN NPs at the IC50, significantly decreased colony formation, induced apoptosis and slowed spheroid growth in vitro. In addition, H-Ras membrane localisation was significantly reduced in the RALA/ALN groups compared to ALN or controls, indicative of prenylation inhibition. The RALA/ALN NPs were lyophilised to enhance stability without compromising the physiochemical properties necessary for functionality, highlighting the suitability of the NPs for scale-up and in vivo application. Collectively, these data show the significant potential of RALA/ALN NPs as novel therapeutics in the treatment of GBM.

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Section: Discussionmentioning

confidence: 99%

Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme

et al. 2021

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“…Most importantly, the responses to NAT in organoids paralleled the patients’ progression-free survival after surgical resection [ 107 ]. Similarly, Di-Liello and colleagues utilized a lung cancer spheroid model to show their utility in predicting the response to chemo and immune therapies [ 108 ]. These studies represent a significant advance in utilization of organoid cultures as a functional tool in predicting response to treatment and could be leveraged by clinicians to personalize therapies.…”

Section: Applications Of Patient-derived Organoids and Spheroidsmentioning

confidence: 99%

Organoid and Spheroid Tumor Models: Techniques and Applications

Gunti

Hoke

et al. 2021

Cancers

255

205

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Techniques to develop three-dimensional cell culture models are rapidly expanding to bridge the gap between conventional cell culture and animal models. Organoid and spheroid cultures have distinct and overlapping purposes and differ in cellular sources and protocol for establishment. Spheroids are of lower complexity structurally but are simple and popular models for drug screening. Organoids histologically and genetically resemble the original tumor from which they were derived. Ease of generation, ability for long-term culture and cryopreservation make organoids suitable for a wide range of applications. Organoids-on-chip models combine organoid methods with powerful designing and fabrication of micro-chip technology. Organoid-chip models can emulate the dynamic microenvironment of tumor pathophysiology as well as tissue–tissue interactions. In this review, we outline different tumor spheroid and organoid models and techniques to establish them. We also discuss the recent advances and applications of tumor organoids with an emphasis on tumor modeling, drug screening, personalized medicine and immunotherapy.

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“…Di Liello et al could demonstrate a reproduction of patient tumor response to chemotherapy by using a spheroid model derived from a non-small cell lung cancer biopsy. This model of spheroid was generated from the cell suspension from the tumor digestion culture on an extracellular matrix (Matrigel) ( 48 ). Although tissue digestion preserves tumor cell interaction, the architecture of the tissue is lost and the loss of stromal cells.…”

Section: D Modelsmentioning

confidence: 99%

3D Tumor Models and Their Use for the Testing of Immunotherapies

Boucherit¹,

Gorvel²,

Olive³

2020

Front. Immunol.

109

100

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Over the past decade, immunotherapy has become a powerful and evident tool in the fight against cancers. Notably, the rise of checkpoint blockade using monoclonal antibodies (anti-CTLA4, anti-PD1) to avoid interaction between inhibitory molecules allowed the betterment of patient care. Indeed, immunotherapies led to increased overall survival in forms of cutaneous melanoma or lung cancer. However, the percentage of patients responding varies from 20 to 40% depending on the type of cancer and on the expression of the target molecules by the tumor. This is due to the tumor microenvironment which allows the acquisition of resistance mechanisms to immunotherapies by tumor cells. These are closely linked to the architecture and cellular composition of the tumor microenvironment. This one acts on different parameters such as the immune cells infiltrate its composition and therefore, favors the recruitment of immunosuppressive cells as well as the tumor expression of checkpoint inhibitors such as Programmed Death Ligand-1 (PD-L1). Therefore, the analysis and modeling of the complexity of the microenvironment is an important parameter to consider, not only in the search for new therapies but also for the identification and stratification of patients likely to respond to immunotherapy. This is why the use of 3D culture models, reflecting the architecture and cellular composition of a tumor, is essential in immuno-oncology studies. Nowadays, there are several 3-D culture methods such as spheroids and organoids, which are applicable to immuno-oncology. In this review we evaluate 3D culture models as tools for the development of treatments in the field of immuno-oncology.

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Ex vivo lung cancer spheroids resemble treatment response of a patient with NSCLC to chemotherapy and immunotherapy: case report and translational study

Cited by 32 publications

References 18 publications

Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme

Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme

Organoid and Spheroid Tumor Models: Techniques and Applications

3D Tumor Models and Their Use for the Testing of Immunotherapies

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