Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML).The role of p53 and PML in regulating cytotoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Furthermore, H-1 PV infection was combined with cytostatic drug treatment.While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis, the cytotoxicity of H-1 PV was more pronounced in p53-negative than in p…

Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors.

Autonomous parvoviruses preferentially replicate in and kill in vitro–transformed cells and reduce the incidence of spontaneous and implanted tumors in animals. Because of these natural oncotropic and oncolytic properties, parvoviruses deserve to be considered as potential antitumor vectors. Here, we assessed whether parvovirus H1 is able to kill human hepatoma cells by induction of apoptosis but spares primary human liver cells, and whether the former cells can efficiently be transduced by H1 virus–based vectors. Cell death, infectivity, and transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells and in primary human hepatocytes with natural and recombinant H1 virus. All h…

Address: 1I. Medical Department, University of Mainz, Langenbeckstr.1, D-55101 Mainz, Germany, 2Deutsches Krebsforschungszentrum, Applied Tumor Virology, Dept. F0100, and Institut National de la Sante et de la Recherche Medicale Unite 375, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany, 3III. Medical Department, University of Mainz, Langenbeckstr.1, D-55101 Mainz, Germany and 4Med. Department Mitte, Klinikum Dortmund GmbH, Beurhausstr. 10, 44137 Dortmund, Germany

Oncolytic parvovirus H1 induces release of heat-shock protein HSP72 in susceptible human tumor cells but may not affect primary immune cells.

Certain autonomous parvoviruses preferentially replicate in and kill in vitro-transformed cells and may reduce the incidence of spontaneous and implanted tumors in animals. Hence, these viruses and their derivatives are currently under evaluation as antitumor vectors. However, the mechanisms underlying their tumor-suppressing properties are not yet understood. We asked whether the lytic parvovirus H1 may enhance the immunogenicity of infected tumor cells. Out of human melanoma and gastrointestinal tumor cells, we selected the cell line SK29-Mel-1 being very susceptible to H1-induced apoptotic killing. Here, no upregulation of HLA class I and costimulatory molecules could be observed followi…

Parvovirus H-1-Induced Tumor Cell Death Enhances Human Immune Response In Vitro via Increased Phagocytosis, Maturation, and Cross-Presentation by Dendritic Cells

Oncotropic and oncolytic viruses have attracted high attention as antitumor agents because they preferentially kill cancer cells in vitro and reduce the incidence of spontaneous, induced, or implanted animal tumors. Some autonomous parvoviruses (H-1, minute virus of mice) and derived recombinant vectors are currently under preclinical evaluation. Still not fully understood, their antitumor properties involve more than just tumor cell killing. Because wild-type parvovirus-mediated tumor cell lysates (TCLs) may trigger antigen-presenting cells (APCs) to augment the host immune repertoire, we analyzed phagocytosis, maturation, and crosspresentation of H-1-induced TCLs by human dendritic cells …