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Toxicological and bio-distribution profile of a GM-CSF-expressing, double-targeted, chimeric oncolytic adenovirus ONCOS-102 – Support for clinical studies on advanced cancer treatment

The purpose of this work was to carry out preclinical toxicity and bio-distribution studies required for regulatory approval of a clinical trial application for Phase I clinical studies of ONCOS-102 (Ad5/3-D24-GM-CSF) for therapy of advanced cancers (NCT01598129). The study design, route of administration and dosage differs from the clinical protocol and in more detail, investigate ...

Causes of death in patients with extranodal cancer of unknown primary: searching for the primary site

Background Cancer of unknown primary (CUP) is a fatal cancer, accounting for 3–5% of all diagnosed cancers. Finding the primary site is important for therapeutic choices and we believe that the organ which is designated as the cause of death may give clues about the primary site. Methods A total of 20,570 patients with CUP were identified from the Swedish Family-Cancer Database. ...

Attenuated Semliki Forest virus for cancer treatment in dogs: safety assessment in two laboratory Beagles

Background Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus ...

Favorable Alteration of Tumor Microenvironment by Immunomodulatory Cytokines for Efficient T-Cell Therapy in Solid Tumors

Unfavorable ratios between the number and activation status of effector and suppressor immune cells infiltrating the tumor contribute to resistance of solid tumors to T-cell based therapies. Here, we studied the capacity of FDA and EMA approved recombinant cytokines to manipulate this balance in favor of efficient anti-tumor responses in B16.OVA melanoma bearing C57BL/6 mice. ...

Incomplete but Infectious Vaccinia Virions Are Produced in the Absence of Oncolysis in Feline SCCF1 Cells

Vaccinia virus is a large, enveloped virus of the poxvirus family. It has broad tropism and typically virus replication culminates in accumulation and lytic release of intracellular mature virus (IMV), the most abundant form of infectious virus, as well as release by budding of extracellular enveloped virus (EEV). Vaccinia viruses have been modified to replicate selectively in ...

Phase I study with ONCOS-102 for the treatment of solid tumors – an evaluation of clinical response and exploratory analyses of immune markers

Background We conducted a phase I study with a granulocyte macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, ONCOS-102, in patients with solid tumors refractory to available treatments. The objectives of the study were to determine the optimal dose for further use and to assess the safety, tolerability and adverse event (AE) profile of ONCOS-102. ...

Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer

Background Cancer of unknown primary site (CUP) is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. Methods 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the ...

Mutation of the Fiber Shaft Heparan Sulphate Binding Site of a 5/3 Chimeric Adenovirus Reduces Liver Tropism

Natural tropism to the liver is a major obstacle in systemic delivery of adenoviruses in cancer gene therapy. Adenovirus binding to soluble coagulation factors and to cellular heparan sulphate proteoglycans via the fiber shaft KKTK domain are suggested to cause liver tropism. Serotype 5 adenovirus constructs with mutated KKTK regions exhibit liver detargeting, but they also ...

Fc-gamma receptor polymorphisms as predictive and prognostic factors in patients receiving oncolytic adenovirus treatment

Background Oncolytic viruses have shown potential as cancer therapeutics, but not all patients seem to benefit from therapy. Polymorphisms in Fc gamma receptors (FcgRs) lead to altered binding affinity of IgG between the receptor allotypes and therefore contribute to differences in immune defense mechanisms. Associations have been identified between FcgR polymorphisms and ...

MicroRNA-Mediated Suppression of Oncolytic Adenovirus Replication in Human Liver

MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression that can suppress their target genes by translational inhibition as well as mRNA destruction. Cell type-specific miRNA expression patterns have been successfully exploited for targeting the expression of experimental and therapeutic gene constructs, for example to reduce pathogenic effects of cancer ...

Anti-Tumor Activity of a miR-199-dependent Oncolytic Adenovirus

Elisa Callegari Bahaeldin K. Elamin Lucilla D'Abundo Simonetta Falzoni Giovanna Donvito Farzaneh Moshiri Maddalena Milazzo Giuseppe Altavilla Luciano Giacomelli Francesca Fornari Akseli Hemminki Francesco

Optimized Mouse Model for the Imaging of Tumor Metastasis upon Experimental Therapy

Development of new cancer treatments focuses increasingly on the relation of cancer tissue with its microenvironment. A major obstacle for the development of new anti-cancer therapies has been the lack of relevant animal models that would reproduce all the events involved in disease progression from the early-stage primary tumor until the development of mature metastatic tissue. To ...

SPECT/CT Imaging of hNIS -Expression after Intravenous Delivery of an Oncolytic Adenovirus and 131I

), Academy of Finland (www.aka.fi), Biocentrum Helsinki (www.helsinki.fi/biocentrum), Biocenter Finland (www. biocenter.fi) and University of Helsinki (www.helsinki.fi). Akseli Hemminki is K. Albin Johansson

Defects in Innate Immunity Render Breast Cancer Initiating Cells Permissive to Oncolytic Adenovirus

Vincenzo Cerullo 0 Akseli Hemminki 0 Maciej Lesniak, The University of Chicago, United States of America 0 1 Transplantation Laboratory, Cancer Gene Therapy Group, Molecular Cancer Biology Program, Haartman

Calcium Gluconate in Phosphate Buffered Saline Increases Gene Delivery with Adenovirus Type 5

Hemminki 0 Paul Cobine, Auburn University, United States of America 0 1 Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory and Haartman Institute and Finnish