Preclinical immunotherapy with Cytokine-Induced Killer lymphocytes against epithelial ovarian cancer

• Published in: Scientific reports Vol. 10; no. 1; p. 6478
• Main Authors: Capellero, S., Erriquez, J., Melano, C., Mesiano, G., Genta, S., Pisacane, A., Mittica, G., Ghisoni, E., Olivero, M., Di Renzo, M. F., Aglietta, M., Sangiolo, D., Valabrega, G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-04-2020; Nature Publishing Group
• Subjects: 59/5; 64; 64/60; 692/4028/67/1517/1709; 692/4028/67/580; 82; 82/1; 82/51; Aged; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumor activity; Ascites; Carboplatin; Carboplatin - pharmacology; Carboplatin - therapeutic use; Carcinoma, Ovarian Epithelial - blood; Carcinoma, Ovarian Epithelial - immunology; Carcinoma, Ovarian Epithelial - pathology; Carcinoma, Ovarian Epithelial - therapy; Cell Line, Tumor; Cytokine-Induced Killer Cells - immunology; Cytokines; Drug Resistance, Neoplasm; Female; Humanities and Social Sciences; Humans; Immunotherapy; Immunotherapy - methods; Lymphocytes; Malignancy; Medical treatment; Metastases; Mice; Middle Aged; multidisciplinary; Ovarian cancer; Ovarian Neoplasms - blood; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Ovary - pathology; Patients; Peripheral blood; Platinum; Primary Cell Culture; Science; Science (multidisciplinary); Surgery; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-63634-z

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.