Surgery, 2020-01, Vol.167 (1), p.197-203
2020
Details
- Autor(en) / Beteiligte
- Titel
- A growth model of neuroendocrine tumor surrogates and the efficacy of a novel somatostatin-receptor–guided antibody-drug conjugate: Perspectives on clinical response?
- Ist Teil von
- Surgery, 2020-01, Vol.167 (1), p.197-203
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- As patient-derived xenografts and other preclinical models of neuroendocrine tumors for testing personalized therapeutics are lacking, we have developed a perfused, 3D bioreactor model to culture tumor surrogates from patient-derived neuroendocrine tumors. This work evaluates the duration of surrogate culture and surrogate response to a novel antibody-drug conjugate. Twenty-seven patient-derived neuroendocrine tumors were cultured. Histologic sections of a pancreatic neuroendocrine tumor xenograft (BON-1) tumor were assessed for SSTR2 expression before tumor implantation into 2 bioreactors. One surrogate was treated with an antibody-drug conjugate composed of an anti-mitotic Monomethyl auristatin-E linked to a somatostatin receptor 2 antibody. Viability and therapeutic response were assessed by pre-imaging incubation with IR-783 and the RealTime-Glo AnnexinV Apoptosis and Necrosis Assay (Promega Corporation, Madison, WI) over 6 days. A primary human pancreatic neuroendocrine tumor was evaluated similarly. Mean surrogate growth duration was 34.8 days. Treated BON-1 surrogates exhibited less proliferation (1.2 vs 1.9-fold) and greater apoptosis (1.5 vs 1.1-fold) than controls, whereas treated patient-derived neuroendocrine tumor bioreactors exhibited greater degrees of apoptosis (13- vs 9-fold) and necrosis (2.5- vs 1.6-fold). Patient-derived neuroendocrine tumor surrogates can be cultured reliably within the bioreactor. This model can be used to evaluate the efficacy of antibody-guided chemotherapy ex vivo and may be useful for predicting clinical responses.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0039-6060eISSN: 1532-7361DOI: 10.1016/j.surg.2019.04.073Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8162105
- Format
- –
- Schlagworte
- Animals, Antineoplastic Agents, Immunological - pharmacology, Antineoplastic Agents, Immunological - therapeutic use, Apoptosis - drug effects, Bioreactors, Cell Proliferation - drug effects, Drug Screening Assays, Antitumor - instrumentation, Drug Screening Assays, Antitumor - methods, Humans, Immunoconjugates - pharmacology, Immunoconjugates - therapeutic use, Male, Mice, Molecular Targeted Therapy - methods, Neuroendocrine Tumors - drug therapy, Neuroendocrine Tumors - pathology, Oligopeptides - pharmacology, Oligopeptides - therapeutic use, Pancreatic Neoplasms - drug therapy, Pancreatic Neoplasms - pathology, Primary Cell Culture - instrumentation, Primary Cell Culture - methods, Receptors, Somatostatin - antagonists & inhibitors, Reproducibility of Results, Tumor Cells, Cultured