Oncolytic Virotherapy to Fight Glioblastoma Multiforme

Here we are at the fourteenth episode of Ben Williams’ guide translation project on treatment options for Glioblastoma Multiforme. This is chapter 10 of the guide. There are six more episodes left till the end of this guide translation project at the end of which I will be able to group all these posts into a single publication that will also be downloadable from this website. In this episode we talk about oncological virotherapy and in particular about Poliovirus, Adenovirus, Newcastle Disease Virus, Herpes Virus and Parvovirus used in conjunction with Bevacizumab (Avastin). The advice is once again to use this information to discuss it with the medical team that is following you. You can present them the references to supporting scientific works.
The Glioblastoma.it fundraising campaign for CUSP-ND for Emanuele needs your help. I am trying in different ways to push the local media but it is not enough. In recent days I have been invited to the RADAR radio broadcast of the regional RAI of Friuli Venezia Giulia (Podcast of the Episode of March 9, 2021) and to the Trieste Live broadcast of Tele 4, a local television station (Video Recording of the Episode of March 16, 2021) but we can’t stop. Let us share the link in order to raise awareness in as many people as possible to help. Enjoy the reading!

Genetically modified poliovirus (PVS-RIPO)

In 2015, this phase I study for recurrent glioblastoma at Duke University received considerable public interest when an episode of the television series 60 Minutes reported on it. More specifically, the first two patients treated in this study had fully responded to therapy. As of March 2015 (when the 60-minute special aired) these two complete response patients were still alive and progression-free at 33 and 34 months after treatment. 11 of the 22 patients in the study were still alive, although six of these patients were less than 6 months after treatment. It is important to emphasize that increasing the PVS-RIPO dose failed to improve efficacy and the patients most recently included in the study were treated with a lower dose than that used by the first patients who participated in the study.

Adenovirus DNX-2401

Another viral therapy in phase 1 had impressive results, comparable to the PVS-RIPO study. DNX-2401 is a modified adenovirus that is injected directly into the tumor.
Preliminary results from a phase 1 study at MD Anderson in Houston, Texas were presented at the November 2014 SNO conference in Miami. 37 patients with recurrent high-grade glioma were treated, with no adverse events attributable to the virus reported. So far 3 out of 25 patients have responded to treatment with complete and lasting responses of 42, 32 and 29 months. These three complete responders had vigorous immune responses, with 10-1000-fold increased levels of interleukin-12p70, a cytokine of great importance for type 1 anticancer immune responses.

Newcastle Disease Virus

An alternative approach to vaccine treatment uses viruses. Newcastle disease is a lethal disease of chickens caused by a virus that is harmless to humans, causing only mild transient flu-like symptoms. It was developed as a cancer treatment in Hungary but was largely ignored until recently. Newcastle Disease Virus is currently used in combination with autologous dendritic cell vaccines by the IOZK clinic in Köln, Germany.

Herpes virus

Another virus used in cancer therapy is a modified form of the herpes virus. Initial trials used a version of the retrovirus, which only infects cells that divide when the virus was infused. Subsequent studies used a version of the adenovirus, which infects both dividing and non-dividing cells. Since the herpes virus can be lethal to the brain if it is allowed to proliferate, patients receive ganciclovir, an effective anti-herpes agent, immediately after infusion of the virus. In a study using this technique performed at Mount Sinai Hospital in New York (170), the median survival of 12 patients with recurrent GBM tumors was 59 weeks from treatment, with 50% of patients alive 12 months after treatment. . The authors also reported the absence of toxicity from the treatment, which was a major concern due to significant brain damage found when the procedure was tested on monkeys.
Why there is so much difference from the monkey study results is unclear.
More recent research with the herpes virus has focused on forms of the virus that are designed to maintain the anti-cancer effects of the virus but without its property of producing neurological inflammation. The first use of this modified virus in a clinical trial was in Glasgow, Scotland. Nine patients with recurrent glioblastomas received the virus injected directly into the tumor. Four were alive at the time of preparation of the study report, 14-24 months after treatment (171).

Parvovirus (with bevacizumab)

A summary presented at the 2015 SNO annual meeting (reference 343, abstract ATNT-07) provided some very encouraging preliminary results from the German phase I / II study of parvovirus H-1 (ParvOryx) for recurrent glioblastoma (NCT01301430). The summary reported that six patients included in the study who received a second dose of parvovirus combined with Avastin following relapse after initial study treatment. This second parvovirus injection was based on a compassionate use agreement. These six patients had tumor recurrence between 4 and 12.6 (mean 7.8) months after the first parvovirus injection. They underwent re-resection and a second injection of parvovirus, followed by chemotherapy (n = 1), Avastin (n = 5), or no additional treatment (n = 1). The mean survival of these patients after the second parvovirus injection was 14.7 months (range 9-26 months). Three of the patients were still alive at 9, 11, and 26 months after this second parvovirus injection. For the five patients treated with Avastin after the second parvovirus injection, the results were even better: 3 out of 5 showed “amazing remissions” with an average survival of 15.4 months, impressive for patients on the second or more relapse of glioblastoma.

___

(170) Germano, I. M., et al. Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. Journal of Neuro-oncology, 2003, 65, 279-289. 
(171) Rampling, R. et al. Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Therapy, 2000, Vol. 7, 859-866.
(343) Geletneky, Karsten et al. “ATNT-07 FAVORABLE RESPONSE OF PATIENTS WITH GLIOBLASTOMA AT SECOND OR THIRD RECURRENCE TO REPEATED INJECTION OF ONCOLYTIC PARVOVIRUS H-1 IN COMBINATION WITH BEVACICUMAB.” Neuro-Oncology 17.suppl 5 (2015): v11-v11.

Great! I hope you enjoyed reading, I was as faithful as possible. Soon the next chapter! See you soon!