The next generation oncolytic viruses of Oncos Therapeutics are based on a decade of research at University of Helsinki and elsewhere. The Cancer Gene Therapy Group continues to publish its latest research and findings in cancer virotherapy and has already published more than 130 international peer-reviewed manuscripts and other publications on all areas involving oncolytic viruses including basic, translational and clinical aspects. Many of these papers have been published in the best gene therapy and cancer research journals.
Oncolytic viruses are a natural phenomenon, known for more than a century and researched in clinical trials for decades . Until recent advances in virology their clinical significance has been overshadowed by other cancer treatment modalities. Today, their development progresses rapidly as the need for new cancer treatments is inevitable and molecular medicine has advanced sufficiently to allow rational development of oncolytic viruses into highly precise cancer-busting weapons.
The next generations of oncolytic viruses of Oncos Therapeutics combine several approaches in killing tumor cells:
- Oncolytic replication , , , . Viruses are engineered to selectively replicate by, for example, utilizing p16-Rb pathway defects – common to most or all human cancers – yet maintaining their high oncolytic potency. Based on improved understanding of the versatility of tumors via genome sequencing, it has been suggested that cancer should be targeted with pathway-specific treatments .
- Anti-tumor immunologic response mediated by oncolytic replication, which per se is an immunogenic phenomenon . Lysis of tumor cells releases tumor associated antigens (TAA) for sampling by antigen presenting cells such as dendritic cells (DC). These cells are crucial for mounting immune responses.
- Arming the viruses with selected human-specific transgenes, which are activated selectively in tumor cells, generating high local presence of anti-tumor agents, administration of which is traditionally limited in low systemic dosing. An example is GM-CSF , which further enhances anti-tumor immunity by e.g. recruitment of natural killers (NK), DC, and activation of DCs at the tumor site. This helps overcome the immune suppressive environment of tumors and also has a sustained beneficial effect – in essence an in situ cancer vaccination.
- Use of different serotypes to enhance tumor cell transduction. Serotype 5 adenovirus uses the Coxsackie-adenovirus receptor (CAR) for host cell entry; since CAR is an adhesion molecule it is variably and often low expressed in human cancer cells. It has been shown that serotype 3 adenovirus has a superior tumor cell transduction compared to serotype 5 in many human cancer cell lines. 
- Many different types of oncolytic viruses (e.g. reovirus, vaccinia, herpes, measles and others) have been tested pre-clinically or in clinical trials. Adenoviruses remain among the strongest in their capacity for gene transfer and expression in cancer cells. At the same time, the largest number of patients (>15 000 cancer patients) have been treated with adenovirus -based cancer gene therapy, and therefore a large body of safety data is available , , , . Safety and gene transfer efficacy have also been validated in several randomized trials performed with oncolytic and non-oncolytic adenoviruses . Oncos Therapeutics is building its next generation virus designs by combining established safety with innovations for enhanced efficacy.
- Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther 2007;15:651–9.
- Alemany, R., Balague, C. & Curiel, D.T. Replicative adenoviruses for cancer therapy. Nat Biotechnol 18, 723-727 (2000).
- Nemunaitis, J. Live viruses in cancer treatment. Oncology (Williston Park) 16, 1483-1492; discussion 1495-1487 (2002).
- Vaha-Koskela, M.J., Heikkila, J.E. & Hinkkanen, A.E. Oncolytic viruses in cancer therapy. Cancer Lett 254, 178-216 (2007).
- Kirn, D., Martuza, R.L. & Zwiebel, J. Replication-selective virotherapy for cancer: Biological principles, risk management and future directions. Nat Med 7, 781-787 (2001).
- ASCO 2009 Keynote. Dr Vogelstein. Available at: http://cgap.nci.nih.gov/
- Immonen, A., et al. AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study. Mol Ther 10, 967-972 (2004).
- Kanerva, A. & Hemminki, A. Adenoviruses for treatment of cancer. Ann Med 37, 33-43 (2005).
- Pearson, S., Jia, H. & Kandachi, K. China approves first gene therapy. Nat Biotechnol 22, 3-4 (2004).
- Yu, W. & Fang, H. Clinical trials with oncolytic adenovirus in China. Curr Cancer Drug Targets 7, 141-148 (2007).
- Dranoff, G., GM-CSF-based cancer vaccines. Immunol Rev, 2002. 188: p. 147-54.
- Kanerva, A., et al., Gene transfer to ovarian cancer versus normal tissues with fiber-modified adenoviruses. Mol Ther, 2002. 5(6): p. 695-704.
- Nemunaitis, J., et al. Biomarkers Predict p53 Gene Therapy Efficacy in Recurrent Squamous Cell Carcinoma of Head and Neck. Mol Ther 17, S139 (2009).
- Alemany R, Cascallo M. Oncolytic viruses from the perspective of the immune system.Future Microbiol. 2009 Jun;4:527-36.
Oncos Therapeutics team maintains and writes the oncolytic virus and cancer gene therapy blog with the selected guest contributors at http://oncolyticvirus.wordpress.com. The blog includes science topics.