SpheroTec GmbH

Planegg, Germany

SpheroTec GmbH

Planegg, Germany
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Halfter K.,SpheroTec GmbH | Mayer B.,SpheroTec GmbH | Mayer B.,Hospital of the LMU Munich
Biotechnology Journal | Year: 2017

Current decision-guiding algorithms in cancer drug treatment are based on decades of research and numerous clinical trials. For the majority of patients, this data is successfully applied for a systemic disease management. For a number of patients however, treatment stratification according to clinically based risk criteria will not be sufficient. The most effective treatment options are ideally identified prior to the start of clinical drug therapy. This review will discuss the implementation of three-dimensional (3D) cell culture models as a preclinical testing paradigm for the efficacy of clinical cancer treatment. Patient tumor-derived cells in 3D cultures duplicate the individual tumor microenvironment with a minimum of confounding factors. Clinical implementation of such personalized tumor models requires a high quality of methodological and clinical validation comparable to other biomarkers. A non-systematic literature search demonstrated the small number of prospective studies that have been conducted in this area of research. This may explain the current reluctance of many physicians and insurance providers in implementing this type of assay into the clinical diagnostic routine despite potential benefit for patients. Achieving valid and reproducible results with a high level of evidence is central in improving the acceptance of preclinical 3D tumor models. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


PubMed | SpheroTec GmbH, Hospital of the LMU Munich, Klinikum Harlaching, Ludwig Maximilians University of Munich and 2 more.
Type: Journal Article | Journal: Journal of translational medicine | Year: 2016

Targeted anti-HER2 therapy has greatly improved the prognosis for many breast cancer patients. However, treatment for HER2 negative disease is currently still selected from a multitude of untargeted chemotherapeutic treatment options. A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients.Tumor samples from 120 HER2 negative patients obtained through biopsy or surgical excision were tested in the breast cancer spheroid model using scaffold-free cell culture. Similarly, spheroids were also generated from established HER2 negative breast cancer cell lines T-47D, MCF7, HCC1143, and HCC1937 to compare treatment efficacy of heterogeneous cell populations from patient tumor tissue with homogeneous cell lines. Spheroids were treated in vitro with guideline-recommended compounds. Treatment mediated impact on cell survival was subsequently quantified using an ATP assay.Differences were observed in the metabolic activity of the untreated spheroids, whereby cell lines consistently achieved higher values compared to tissue spheroids (p<0.001). A higher number of cells per spheroid correlated with a higher basal metabolic activity in tissue-derived spheroids (p<0.01), while the opposite was observed for cell line spheroids (p<0.01). Recurrent tumors showed a higher mean vitality (p<0.01) compared to primary tumors. Except for taxanes, treatment efficacy for most tested compounds differed significantly between breast cancer tissue spheroids and breast cancer cell lines. Overall a high variability in treatment response in vitro was seen in the tissue spheroids regardless of the tested substances. A greater response to anthracycline/docetaxel was observed for hormone receptor negative samples (p<0.01). A higher response to 5-FU (p<0.01) and anthracycline (p<0.05) was seen in high grade tumors. Smaller tumor size and negative lymph node status were both associated with a higher treatment efficacy to anthracycline treatment combined with 5-FU (cT1/2 vs cT3/4, p=0.035, cN+vs cN-, p<0.05).The tissue spheroid model reflects current guideline treatment recommendations for HER2 negative breast cancer, whereas tested cell lines did not. This model represents a unique diagnostic method to select the most effective therapy out of several equivalent treatment options.


Hoffmann O.I.,SpheroTec GmbH | Ilmberger C.,SpheroTec GmbH | Magosch S.,SpheroTec GmbH | Joka M.,Ludwig Maximilians University of Munich | And 3 more authors.
Journal of Biotechnology | Year: 2015

Pharmaceutical investigators are searching for preclinical models closely resembling the original cancer and predicting clinical outcome. This study compares drug response of three in vitro 3D-drug screening models with different complexity.Tumor cell line spheroids were generated from the cell lines Caco-2, DLD-1, COLO 205, HT-29 and HCT-116, and treated with clinically relevant combination therapies, namely 5-FU/oxaliplatin (FO), 5-FU/irinotecan (FI) and the molecular drugs Cetuximab, Trastuzumab, Vorinostat and Everolimus. Treatment results were compared with spheroids originated from tumor cell lines (Caco-2, DLD-1) co-cultured with stromal cells (PBMCs, cancer-associated fibroblasts of colorectal origin) and spheroids directly prepared from colon cancer tissues.Different microenvironment compositions altered the tumor cell line spheroid response patterns. Adding PBMCs increased resistance to FO treatment by 10-15% in Caco-2 and DLD-1 spheroids but decreased resistance to FI by 16% in DLD-1 spheroids. Fibroblast co-cultures decreased resistance to FI in Caco-2 spheroids by 38% but had no impact on FO. Treatment of colon cancer tissue spheroids revealed three distinct response pattern subgroups not detectable in 3D cell lines models.The cancer tissue spheroid model mimics both tumor characteristics and the stromal microenvironment and therefore is an invaluable screening model for pharmaceutical drug development. © 2015 The Authors.


Patent
SpheroTec GmbH | Date: 2015-05-11

The invention relates to a process for generating fibroblasts, more particularly, to the culturing of fibroblasts in large numbers and of the heterogenic type. The invention is also directed to the use of fibroblasts in the preparation of heterotypic spheroids and a process for the preparation of such heterotypic spheroids.


Patent
SpheroTec GmbH | Date: 2015-09-07

The invention pertains to a process for the preparation of multicellular spheroids from a suspension of single cells, wherein the cells are directly derived from a biological tissue and/or from cell-containing bodily fluid. The invention is further directed to the multicellular spheroids obtained by the process according to the invention as well as to the use of the spheroids for diagnostic, screening and therapeutic purposes.


Patent
SpheroTec GmbH | Date: 2010-06-23

The invention relates to a process for generating fibroblasts, more particularly, to the culturing of fibroblasts in large numbers and of the heterogenic type. The invention is also directed to the use of fibroblasts in the preparation of heterotypic spheroids and a process for the preparation of such heterotypic spheroids.


PubMed | SpheroTec GmbH
Type: | Journal: Biotechnology journal | Year: 2017

Current decision-guiding algorithms in cancer drug treatment are based on decades of research and numerous clinical trials. For the majority of patients, this data is successfully applied for a systemic disease management. For a number of patients however, treatment stratification according to clinically based risk criteria will not be sufficient. The most effective treatment options are ideally identified prior to the start of clinical drug therapy. This review will discuss the implementation of three-dimensional (3D) cell culture models as a preclinical testing paradigm for the efficacy of clinical cancer treatment. Patient tumor-derived cells in 3D cultures duplicate the individual tumor microenvironment with a minimum of confounding factors. Clinical implementation of such personalized tumor models requires a high quality of methodological and clinical validation comparable to other biomarkers. A non-systematic literature search demonstrated the small number of prospective studies that have been conducted in this area of research. This may explain the current reluctance of many physicians and insurance providers in implementing this type of assay into the clinical diagnostic routine despite potential benefit for patients. Achieving valid and reproducible results with a high level of evidence is central in improving the acceptance of preclinical 3D tumor models.


The invention relates to methods for testing the response of spheroids to exposure with therapeutics. Preferably the spheroids are derived from primary isolate biological tissue and/or cell-containing bodily fluid. Further embodiments relate to spheroid sections and arrays including kits suitable for carrying out the method according to the present invention.


PubMed | Martin Luther University of Halle Wittenberg, University of Ulm and Spherotec GmbH
Type: Journal Article | Journal: Proteomics | Year: 2016

Tyrosine kinase inhibitors, such as erlotinib, display reliable responses and survival benefits for the treatment of human non-small cell lung cancer (NSCLC) patients. However, primary or acquired resistance limits their therapeutic success. In this study, we conducted in-depth mass spectrometric analyses of NSCLC cell secretomes. To identify secreted proteins that are differentially regulated in erlotinib-sensitive (PC-9) and -resistant (PC-9ER) NSCLC cell lines, SILAC experiments were performed. On average, 900 proteins were identified in each sample with low variations in the numbers of identified proteins. Fourteen proteins were found to be differently regulated among erlotinib-sensitive and -resistant NSCLC cell lines, with five proteins (tissue-type plasminogen activator, epidermal growth factor receptor, urokinase-type plasminogen activator, platelet-derived growth factor D, and myeloid-derived growth factor) showing the most prominent regulation. Tissue-type plasminogen activator (t-PA) was up to 10-times upregulated in erlotinib-resistant NSCLC cells compared with erlotinib-sensitive cells. T-PA is an established tumor marker for various cancer types and seems to be a promising prognostic marker to differentiate erlotinib-sensitive from erlotinib-resistant NSCLC cells. To gain further insights into t-PA-regulated pathways, a t-PA variant was expressed in E. coli cells and its interactions with proteins secreted from erlotinib-sensitive and -resistant NCSLC cells were studied by a combined affinity enrichment chemical cross-linking/mass spectrometry (MS) approach. Fourteen proteins were identified as potential t-PA interaction partners, deserving a closer inspection to unravel the mechanisms underlying erlotinib resistance in NSCLC cells.


PubMed | Ludwig Maximilians University of Munich and SpheroTec GmbH
Type: | Journal: Journal of biotechnology | Year: 2015

Pharmaceutical investigators are searching for preclinical models closely resembling the original cancer and predicting clinical outcome. This study compares drug response of three in vitro 3D-drug screening models with different complexity. Tumor cell line spheroids were generated from the cell lines Caco-2, DLD-1, COLO 205, HT-29 and HCT-116, and treated with clinically relevant combination therapies, namely 5-FU/oxaliplatin (FO), 5-FU/irinotecan (FI) and the molecular drugs Cetuximab, Trastuzumab, Vorinostat and Everolimus. Treatment results were compared with spheroids originated from tumor cell lines (Caco-2, DLD-1) co-cultured with stromal cells (PBMCs, cancer-associated fibroblasts of colorectal origin) and spheroids directly prepared from colon cancer tissues. Different microenvironment compositions altered the tumor cell line spheroid response patterns. Adding PBMCs increased resistance to FO treatment by 10-15% in Caco-2 and DLD-1 spheroids but decreased resistance to FI by 16% in DLD-1 spheroids. Fibroblast co-cultures decreased resistance to FI in Caco-2 spheroids by 38% but had no impact on FO. Treatment of colon cancer tissue spheroids revealed three distinct response pattern subgroups not detectable in 3D cell lines models. The cancer tissue spheroid model mimics both tumor characteristics and the stromal microenvironment and therefore is an invaluable screening model for pharmaceutical drug development.

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