The combination of MEK inhibitor and anti PD-L1: Effects on organoid models from NSCLC biopsies

Corte, Carminia Maria Della; Barra, G.; Ciaramella, Vincenza; Liello, Raimondo Di; Fasano, Morena; Ciardiello, F.; Morgillo, Floriana

doi:10.1093/annonc/mdy303.021

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“…Similarly, we also tested pembrolizumab and found that it reduced the viability of tumour spheroids in a dose-dependent manner, reaching the maximum of antiproliferative activity at 10 µg/mL dose (figure 3D), which correspond to the therapeutic dose for clinical use of pembrolizumab 8 9. Of interest, reverse transcription-PCR on messenger RNA extract from treated spheroids confirmed an increased transcript of interferon-γ and CD107a upregulation (a degranulation marker) after pembrolizumab treatment, thus, confirming an engagement of infiltrating T cells in this response 10…”

Section: Features and Drug Sensitivity Of Patient-derived Spheroidsmentioning

confidence: 57%

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

et al. 2019

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IntroductionIn the era of precision medicine, research studies are aiming to design patient-tailored treatment strategies. In this work, we present a clinical case of a patient with non-small cell lung cancer (NSCLC) accompanied by a translational study with the intent to assess the correspondence of drug sensitivity in ex vivo spheroidal tumour cultures and peripheral blood biomarkers with clinical outcome.MethodsPrimary tumour tissue, patient-derived tumour spheroids, peripheral blood mononuclear cells and circulating DNA were analysed to assess drug sensitivity and immunological profiling, and all these data were correlated with clinical and radiological evaluations.ResultsImmunohistochemistry, immunofluorescence, next generation sequencing analysis and T-lymphocyte receptor repertoire assay results showed elevated concordance among primary tumour tissue, ex vivo three-dimensional tumour spheroid specimen and circulating DNA. Cisplatin-based chemotherapy and anti-programmed death 1 drug sensitivity assessed in spheroidal cultures were strictly consistent with patient clinical response to adjuvant chemotherapy and first-line immune therapy.ConclusionThese results revealed that ex vivo drug sensitivity testing in three-dimensional spheroidal culture can reproduce clinical response to chemotherapy and immunotherapy, with the potential to use those culture models to predict patients‘ outcome from anticancer treatments and, therefore, the feasibility to select individualised therapy.

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Section: Features and Drug Sensitivity Of Patient-derived Spheroidsmentioning

confidence: 57%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

The combination of MEK inhibitor and anti PD-L1: Effects on organoid models from NSCLC biopsies

Cited by 1 publication

References 0 publications

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

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

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