Oncolytic adenovirus treatment of a patient with refractory neuroblastoma

Sari Pesonen Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Heikki Helin HUSLAB, Helsinki University Central Hospital, Finland; Department of Pathology, Helsinki University Central Hospital, Finland

Petri Nokisalmi Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Sophie Escutenaire Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Camilla Ribacka Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Merja Sarkioja Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Vincenzo Cerullo Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Kilian Guse Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Gerd Bauerschmitz Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland; Department of Obstetrics and Gynecology, Duesseldorf University Medical Center, Heinrich-Heine University, Germany

Leena Laasonen Helsinki Medical Imaging Center, University of Helsinki, Finland

Teemu Kantola Department of Anesthesiology, Helsinki University Central Hospital, Finland

Ari Ristimaki Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Department of Pathology, Helsinki University Central Hospital, Finland; Genome Scale Biology Program, Biomedicum Helsinki, Finland

Maria Rajecki Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Minna Oksanen Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Elina Haavisto Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland

Anna Kanerva Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland and

Timo Joensuu Docrates Oncology Hospital, Helsinki, Finland

Akseli Hemminki Cancer Gene Therapy Group, Transplantation Laboratory and Finnish Institute of Molecular Medicine, University of Helsinki, Finland; Haartman Institute, University of Helsinki, FinlandCorrespondence[email protected]

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Figures & data

Figure 1. A chemotherapy resistant case of neuroblastoma was treated with oncolytic adenovirus Ad5/3-Cox2L-D24. A) Computer tomography of primary tumor before oncolytic virus treatment. B) Magnetic resonance imaging one month after treatment shows moderate decrease of the primary tumor and complete regression of the lymph nodes. C) Before treatment, bone marrow was almost completely infiltrated by neuroblastoma cells (CD56 staining, brown, 10x), (monoclonal mouse anti-SCLC (CD56, N-CAM), Clone 123C3, Invitrogen, CA, USA). D) Few neuroblastoma cells in bone marrow three months after oncolytic virus treatment (10x). E) Oncolytic virus treatment increased the number of CD3+/CD8+ cytotoxic T-cells in blood. F) Anti-adenoviral neutralizing antibodies were induced. G) Virus was detected in blood for three weeks after treatment. H) Immunohistochemistry indicated intermediate Cox2 expression (brown, 20x) in tumor cells (monoclonal mouse anti-human Cox-2, Clone CX229, Cayman Chemical, MI, USA).

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