Treatment approaches combining cytostatic drugs with the oncolytic parvovirus H-1 increase cytotoxic effects in cell culture models of highly malignant pediatric brain tumors

• Published in: Klinische Pädiatrie
• Main Authors: Westphal, C, Öztürk, S, Josupeit, R, Leuchs, B, Witt, O, Rommelaere, J, Lacroix, J
• Format: Conference Proceeding
• Language: English; German
• Published: 16.12.2014
• ISSN: 0300-8630; 1439-3824
• DOI: 10.1055/s-0034-1393947

Oncolytic virotherapy with Parvovirus H-1 (H-1PV) represents a new therapeutic approach investigated in a phase I/IIa clinical trial recruiting adult glioblastoma patients. In pediatric neurooncology there is also an urgent need for new therapeutic options. In vitro H-1PV has already been demonstrated to induce cytotoxic effects in medulloblastoma and pediatric glioblastoma. However, the application of combination therapies is inevitable to avoid the development of resistant subclones of cancer cells. Here we analyzed, whether H-1PV is able to increase the cytotoxic efficacy of conventional cytostatic treatment of highly malignant pediatric brain cancer cells. Pediatric medulloblastoma (n = 6) and pediatric glioblastoma (n = 4) cell lines were treated with H-1PV, temozolomide, carboplatin or etoposide to determine the median lethal doses for each agent. Sublethal doses of each of these drugs were subsequently used to test the cytotoxic efficacy of combination treatment approaches. No inhibitory effects of the cytostatic drugs on H-1PV entry and transduction have been observed. In pediatric glioblastoma cell culture models additive cytotoxic effects were observed after combined administration of H-1PV and temozolomide. In the medulloblastoma cell line most resistant to H-1PV infection combinatorial treatment with H-1PV significantly improved cytotoxic effects induced by etoposide or carboplatin. Individual combinations of conventional cytostatic drugs with H-1PV induced complete cell lysis in all pediatric medulloblastoma and glioblastoma cell lines tested.