MTO: a new journal for a maturing field

The association between natural viral infection and remission of cancer has been described for over a 100 years.¹ The clinical observations that microbial infection of tumor may produce direct killing of cancer or through host immune actions are the basis of the field of oncolytic viral therapy. Astute investigators in the 1950’s through the 1960’s attempted to capitalize on such observations with preclinical and clinical testing of natural viruses as anticancer agents. Efforts such as those at the clinic at the Memorial Sloan-Kettering Cancer Center led by Southam or at the National Institutes of Health led by Shimkin elucidated much of the clinical knowledge of oncolytic therapy that is the foundations of this field.² In New York, Dr Southam treated thousands of cancer patients.³ The field was forced into a hiatus in the 1970’s when these viruses proved too toxic at doses effective for killing cancer. This is not surprising, since the most effective oncolytic viruses included very pathogenic viruses such as measles and West Nile Virus. The development of refined methods of genetic engineering of both DNA and RNA viruses has brought resurgence in this field. The last three decades have seen a rebirth of oncolytic therapy exemplified by the E1B-deleted adenoviruses of McCormack⁴ and the γ 34.5-deleted herpes simplex viruses of Roizman⁵ and Martuza.⁶ The current generation of engineered oncolytic viruses is highly selective for replication in cancer cells. They can also carry genetic payloads encoding other anticancer proteins for deployment at tumor sites. One such agent is already approved in China for treatment of head and neck cancer.⁷ It is likely that others will soon be approved in the United States or Europe.

This resurgence in virally based oncolytic therapy coincides with mounting enthusiasm in engineered cell-based oncolytic therapy. Recent work in genetically modified stem cells that have tropism and killing activity for cancer,⁸ as well as tumoricidal successes both in tumor specific immune cells⁹ and chimeric antigen receptor T cells¹⁰ have engendered scientific and industrial interest.

This summer, the American Society of Gene & Cell Therapy in partnership with Nature Publishing Group will launch the journal Molecular Therapy – Oncolytics (MTO). The new journal signals mainstream acceptance of this maturing field. It will publish papers that involve “engineering cells, viruses, or other microorganisms to combat cancer.” As is the case with its sister Molecular Therapy journals, MTO will aim to uphold the standards of the sponsoring American Society of Gene and Cell Therapy. It will aim for rapid publication of new knowledge to facilitate treatment and cure of human cancer.

For any gene therapy to reach patients requires not only the underlying basic science, but also engineering and optimization of agent production, preclinical testing, financing, negotiation of regulatory hurdles, and completion of well-designed and controlled trials. Valuable data along any of these steps will help speed novel viral therapies to patients with life spans otherwise shortened by advanced cancer. Gene therapy journals must therefore publish both basic and translational studies. Publications describing advances in production methodology or preclinical toxicology for each virus or cell line will pave the way for optimization of platforms that produce the most selective therapies, with the least toxicity, and at the lowest cost. The availability of a menu of optimized viral, bacterial, or cell platform should allow clinicians to select trial agents on a more rational basis according to the type of cancer, the targeted cellular mechanisms, and the site of disease.

In addition, the online publication format of the new journal obviates the limitation of physical journal pages and will thus allow inclusion of useful appendices with detailed data from preclinical and clinical trials. Easy availability of this large amount of primary data should facilitate approval of trials of similar agents in a more expeditious and less expensive manner. The format is also well suited to the publication of so-called negative data, in the form of reports of “no dose-limiting toxicity,” “no shedding,” “no latency,” or “no reactivation.” It is hoped that investigators will relinquish the competitive advantage of holding such data unpublished in order to allow the field to move more quickly.

As the field of Oncolytic Therapy matures, our meetings and journals should see direct comparisons of various oncolytic platforms. There have been few comparative studies to date, likely because most groups are invested professionally or financially in a single platform. However, there is unlikely to be a single preferred platform, but rather each platform is likely to exhibit specific advantages in particular disease settings.

Oncolytic therapy has moved from observations of the early 20th century to the failed trials of natural viruses in the late 20th century and now to rational design of the current generation of promising agents. The next years should see full maturation of this field, including successful clinical trials to establish oncolytic therapies as standard clinical therapies.