原创力文档activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus h-1激活人体免疫系统通过化疗或靶向制剂结合溶瘤细胞的细小病毒h.pdfVIP
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activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus h-1激活人体免疫系统通过化疗或靶向制剂结合溶瘤细胞的细小病毒h
Moehler et al. BMC Cancer 2011, 11:464
/1471-2407/11/464
RESEARCH ARTICLE Open Access
Activation of the human immune system by
chemotherapeutic or targeted agents combined
with the oncolytic parvovirus H-1
1* 1† 1 1 2 1
Markus Moehler , Maike Sieben , Susanne Roth , Franziska Springsguth , Barbara Leuchs , Maja Zeidler ,
Christiane Dinsart2, Jean Rommelaere3 and Peter R Galle1
Abstract
Background: Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric,
colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents
or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV.
Methods: Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced
tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/-
characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC).
Results: H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of 50%, which appeared to occur
primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination
with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation
was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel
lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor
necrosis factor-a and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel
tumor cell lysates (TCL) and was also high with DC-CT
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