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Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5/3-Cox2L-D24 in patients with metastatic and
S Pesonen1, P Nokisalmi, S Escutenaire
1Cancer Gene Therapy Group, Transplantation Laboratory, Haartman Institute and Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.
Abstract:
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.
Insights
The novel oncolytic adenovirus Ad5/3-Cox2L-D24 shows safety in cancer patients, with extended virus circulation after a single treatment. Objective anti-tumor activity was observed in 61% of patients, warranting further clinical trials.
Area of Science:
- Oncolytic virotherapy
- Viral oncology
- Cancer gene therapy
Background:
- Refractory and progressive solid tumors present significant treatment challenges.
- Oncolytic adenoviruses offer a promising therapeutic strategy for cancer.
- Ad5/3-Cox2L-D24 represents a novel adenovirus engineered for enhanced tumor targeting.
Purpose of the Study:
- To evaluate the safety and preliminary efficacy of a single round of Ad5/3-Cox2L-D24 in patients with advanced solid tumors.
- To assess the pharmacokinetic profile and immunogenicity of Ad5/3-Cox2L-D24.
- To determine objective anti-tumor responses using radiological and tumor marker assessments.
Main Methods:
- Eighteen patients with refractory solid tumors received a single dose of Ad5/3-Cox2L-D24.
- Safety was monitored through adverse event reporting and laboratory tests.
- Viral shedding, serum virus presence, neutralizing antibody titers, and tumor responses (RECIST, tumor density, tumor markers) were assessed.
Main Results:
- The treatment was generally well-tolerated, with most side effects being Grade 1-2 flu-like symptoms. One patient experienced Grade 3 ileus.
- High neutralizing antibody titers were observed within 3 weeks, and virus was detected in serum for up to 5 weeks in 83% of patients.
- Objective anti-tumor activity was observed in 11/18 (61%) patients, including partial response (PR) in one patient, minor response (MR) in another, and tumor density reductions in two progressive disease (PD) patients.
Conclusions:
- Ad5/3-Cox2L-D24 demonstrates an acceptable safety profile for human cancer treatment.
- A single administration of Ad5/3-Cox2L-D24 leads to prolonged virus circulation.
- The study provides objective evidence of anti-tumor activity, supporting further clinical investigation.
