Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5 3-Cox2L-D24 in patients with metastatic and refractory solid tumors

• Published in: Gene therapy Vol. 17; no. 7; pp. 892 - 904
• Main Authors: Pesonen, S, Nokisalmi, P, Escutenaire, S, Särkioja, M, Raki, M, Cerullo, V, Kangasniemi, L, Laasonen, L, Ribacka, C, Guse, K, Haavisto, E, Oksanen, M, Rajecki, M, Helminen, A, Ristimäki, A, Karioja-Kallio, A, Karli, E, Kantola, T, Bauerschmitz, G, Kanerva, A, Joensuu, T, Hemminki, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2010; Nature Publishing Group
• Subjects: 631/1647/1511; 631/326/596/1278; 631/67; 692/700/565/1331; Adenoviridae - isolation & purification; Adenovirus; Adenoviruses; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies, Viral; Antitumor agents; Applied cell therapy and gene therapy; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer; Care and treatment; Cell Biology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Child, Preschool; Clinical trials; Cyclooxygenases; Development and progression; Female; Fever; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Therapy; Genetic aspects; Health. Pharmaceutical industry; Human Genetics; Humans; Industrial applications and implications. Economical aspects; Liver - enzymology; Male; Medical sciences; Metastases; Middle Aged; Molecular and cellular biology; Nanotechnology; Neoplasm Metastasis; Neoplasms - blood; Neoplasms - pathology; Neoplasms - therapy; Neoplasms - virology; Oncolysis; Oncolytic Virotherapy - adverse effects; Oncolytic Virotherapy - methods; original-article; Patients; Physiological aspects; Solid tumors; Thrombocytopenia; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Treatment Outcome; Tumor markers; Tumors; Finland; oncolytic adenovirus; cyclooxygenase 2; cancer; Human; Solid tumor; Adenoviridae; Enzyme; Cyclooxygenase 2; Systemic; Metastasis; Malignant tumor; Virus; Adenovirus 3; Human adenovirus; Mastadenovirus; Oxidoreductases; Gene therapy; Vector; Cancer
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2010.17

Eighteen patients with refractory and progressive solid tumors were treated with a single round of triple modified oncolytic adenovirus (Ad5/3-Cox2L-D24). Ad5/3-Cox2L-D24 is the first non-Coxsackie-adenovirus receptor-binding oncolytic adenovirus used in humans. Grades 1–2 flu-like symptoms, fever, and fatigue were seen in most patients, whereas transaminitis or thrombocytopenia were seen in some. Non-hematological grades 3–5 side effects were seen in one patient with grade 3 ileus. Treatment resulted in high neutralizing antibody titers within 3 weeks. Virus appeared in serum 2–4 days after treatment in 83% of patients and persisted for up to 5 weeks. One out of five radiologically evaluable patients had partial response (PR), one had minor response (MR), and three had progressive disease (PD). Two patients scored as PD had a decrease in tumor density. Tumor reductions not measurable with Response Evaluation Criteria In Solid Tumors (RECIST) were seen in a further four patients. PR, MR, stable disease, and PD were seen in 12, 23.5, 35, and 29.5% of tumor markers analyzed, respectively ( N =17). Ad5/3-Cox2L-D24 appears safe for treatment of cancer in humans and extended virus circulation results from a single treatment. Objective evidence of anti-tumor activity was seen in 11/18 (61%) of patients. Clinical trials are needed to extend these findings.