Dr Fueyo and colleagues recently published the results of a phase 1 study in the Journal of Clinical Oncology, which evaluated the antitumor efficacy of a modified version of a common cold virus, DNX-2401 (Delta-24-RGD; tasadenoturev), in patients with glioma.4 The dose-escalation study enrolled 37 patients who received a single intratumoral injection of DNX-2401 (group A). Fourteen of these patients had injection with through a permanently implanted catheter followed by resection after 14 days (group B).
Twenty percent of patients in group A survived longer than 3 years and 3 had more than 95% reduction in tumor volume. Specimen analyses from group B showed that DNX-2401 replicated and spread within the tumor.
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According to Dr Fueyo and Candelaria Gomez-Manzano, MD, also of the MD Anderson Cancer Center, who co-developed the DNX-2401 platform, these results show two types of evidence suggesting that the oncolytic virus induced an antitumor response.
First, the authors discussed a patient treated with a single injection of the virus who had what appeared to be tumor progression on a scan taken at 5 weeks. The tumor was resected and a specimen sent to pathology.
“Pathology showed that 20% of the tumor contained cancer cells, but 80% of the mass was lymphocytes,” Dr Fueyo told Cancer Therapy Advisor. “There was a humungous inflammation within the tumor at the moment of the resection that strongly suggests that there was an immune reaction against the tumor.”
Dr Fueyo and colleagues showed that at least 20% of the patients that survived more than 3 years had changes in radiology that strongly suggested the same inflammation.
“These two things together — the radiologic images showing progression based on inflammation and pathologic confirmation of inflammation in specimens taken from the tumor that were resected — strongly suggest an immune response against the tumor,” said Dr Gomez-Manzano.
Other Considerations
According to Dr Fueyo, while any virus may be able to induce an antitumor immune response, the question will be which is the safest.
“There are new reports about the Zika virus being modified to treat brain tumors,” Dr Fueyo said. “Yet just because we can do it doesn’t mean it is the best approach.”
The cost of oncolytic viral therapy is also a concern for Drs Fueyo and Gomez-Manzano.
Another therapy that harnesses the body’s immune response, chimeric antigen receptor (CAR)-T cell therapy, was recently approved for B-cell acute lymphoblastic leukemia (tisagenlecleucel) and aggressive B-cell non-Hodgkin lymphoma (axicabtagene ciloleucel.) Each dose of CAR-T cell therapy is customized by collecting a patient’s own lymphocytes, modifying them to direct them to attack cancer cells, and infusing them back into the patient. Novartis has set a list price of $475,000 for tisagenlecleucel and Gilead has listed the pricing of axicabtagene ciloleucel at $373,000.5
“It is bad when you are doing research in a lab and trying to develop a treatment and thinking, ‘who is going to be able to pay for this?’” Dr Fueyo said.
“The production of our virus and the final price should, however, be much cheaper than biological therapies like CAR-T cells or immune checkpoint inhibitors.”
References
- FDA approves IMLYGIC™ (talimogene laherparepvec) as first oncolytic viral therapy in the US [news release]. Thousand Oaks, CA: Amgen; October 27, 2015. http://www.amgen.com/media/news-releases/2015/10/fda-approves-imlygic-talimogene-laherparepvec-as-first-oncolytic-viral-therapy-in-the-us/. Accessed February 2018.
- NCI dictionary of cancer terms: oncolytic virus therapy. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oncolytic-virus-therapy. Accessed February 2018.
- Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780-8.
- Lang FE, Conrad C, Gomez-Manzano C, et al. Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J Clin Oncol. 2018 Feb 12. doi: 10.1200/JCO.2017.75.8219 [Epub ahead of print]
- Kite’s Yescarta™ (axicabtagene ciloleucel) becomes first CAR T therapy approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy [news release]. Foster City, CA and Santa Monica, CA: BusinessWire; October 18, 2017. https://www.businesswire.com/news/home/20171018006639/en/Kite%E2%80%99s-Yescarta%E2%84%A2-Axicabtagene-Ciloleucel-CAR-Therapy-Approved. Accessed February 2018.
