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Sci Rep ; 10(1): 6478, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296104

RESUMO

Despite improvements in surgery and medical treatments, epithelial ovarian cancer (EOC) remains the most lethal gynaecological malignancy. Aim of this study is to investigate the preclinical immunotherapy activity of cytokine-induced killer lymphocytes (CIK) against epithelial ovarian cancers, focusing on platinum-resistant settings. We generated CIK ex vivo starting from human peripheral blood samples (PBMCs) collected from EOC patients. Their antitumor activity was tested in vitro and in vivo against platinum-resistant patient-derived ovarian cancer cells (pdOVCs) and a Patient Derived Xenograft (PDX), respectively. CIK were efficiently generated (48 fold median ex vivo expansion) from EOC patients; pdOVCs lines (n = 9) were successfully generated from metastatic ascites; the expression of CIK target molecules by pdOVC confirmed pre and post treatment in vitro with carboplatin. The results indicate that patient-derived CIK effectively killed autologous pdOVCs in vitro. Such intense activity was maintained against a subset of pdOVC that survived in vitro treatment with carboplatin. Moreover, CIK antitumor activity and tumor homing was confirmed in vivo within an EOC PDX model. Our preliminary data suggest that CIK are active in platinum resistant ovarian cancer models and should be therefore further investigated as a new therapeutic option in this extremely challenging setting.


Assuntos
Carcinoma Epitelial do Ovário/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Imunoterapia/métodos , Neoplasias Ovarianas/terapia , Idoso , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carboplatina/farmacologia , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Cultura Primária de Células , Ensaios Antitumorais Modelo de Xenoenxerto
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