I’ve posted extensively about Oncolytic virus trials, focused on the ongoing Neuroendocrine Cancer trial in Uppsala Sweden. I wanted to incorporate this information into a single article ready for future news, whilst at the same time updating you on further developments in the field of Oncolytic Viruses for Neuroendocrine Cancer. The excitement of the Uppsala work has dampened in recent years, not helped by the fact that one of the first patients unfortunately died. In the absence of any news, I suspect there has been no real progress and/or the funding has run out.
What exactly are Oncolytic Viruses?
Oncolytic Viruses infects and breaks down cancer cells but not normal cells. Oncolytic viruses can occur naturally or can be made in the laboratory by changing other viruses. Certain oncolytic viruses are being studied in the treatment of cancer. Some scientists say they are another type of immunotherapy whilst others say it’s too early to classify as such. The good news is that Neuroendocrine Cancer seems to figure in this work with two of these viruses apparently working on mice to date. Listed below are two active projects involving NETs, one directly and one indirectly.
The Uppsala Trial – AdVince
Read here for an update released 7th June 2019.
I’ll briefly describe what’s happening and then you can link to my Facebook article if you need more background.
The trial is called AdVince after Vince Hamilton who funded it. Unfortunately he died before he saw any output but his forward thinking and benevolence lives on and might hopefully help NET patients in the longer term. It’s quite a small trial and is being conducted in Uppsala University Sweden, a famous European NET Centre of Excellence and where many people from across the world attend to take advantage of PRRT availability and experience and is home to famous NET specialist Kjell Öberg, MD, PhD, a professor of endocrine oncology.
A Swedish man (Jan-Erik Jannsson) was the first to get the virus to their cancer (NETs) using a genetically modified virus.
Unfortunately, I was given the news from a source close to the trial that Jan died last year of pneumonia. I have no evidence to suggest his death is in anyway connected to the trial but I’m told he was an ill man prior to the trial commencing. I have therefore dedicated this post to him. RIP Jan.
The initial data presented by the trial indicated that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET. The last I heard from the trial is that they are trying to recruit a further 12 patients to Phase IIa (the trial document allows for up to 36).
Read more background on my Facebook post here: Click here
The trial document on Clinical Trials Website: Click here
Then read this status update from the trial sponsors released in March 2018
Pexa-Vec Oncolytic Virus Trials
This is an oncolytic viral therapy currently in phase III and phase Ib/II clinical trials for use against primary liver (Hepatocellular Carcinoma) and Colorectal cancers, respectively. Pexa-Vec is a weakened (or attenuated) virus that is based on a vaccine used in the eradication of smallpox. The modified virus is injected directly into the cancer tumour, to grow inside these rapidly growing cancer cells and hopefully kill them.
According to the Colorectal Clinical Trial, the aim of the study is to evaluate whether the anti-tumor immunity induced by Pexa-Vec oncolytic viral therapy can be enhanced by immune checkpoint inhibition i.e. they are testing it in conjunction with Immunotherapy drugs (in the case of Colorectal, Durvalumab, and a combination of Durvalumab and Tremelimumab).
The Hepatocellular Carcinoma trial (Phocus) is at Phase III where the sponsors are evaluating Pexa-Vec to determine if it can slow the progression of advanced liver cancer and improve quality of life. I can other trials appearing such as this one for Colorectal Cancer and this one for any solid tumour type.
The work is a collaboration forged between University of California San Francisco (UCSF) vascular researcher Donald McDonald, MD, PhD, and researchers at San Francisco-based biotech SillaJen Biotherapeutics Inc. (formerly Jennerex Biotherapeutics, Inc.), a subsidiary of SillaJen, Inc., headquartered in Korea.
Check out this page: click here
So what’s the Neuroendocrine Connection with Pexa-Vec?
As part of the research, McDonald’s lab injected it intravenously into mice genetically modified to develop pancreatic neuroendocrine cancer. They found that the virus failed to infect healthy organs or make the animals ill, but succeeded in infecting blood vessels within tumors. These initial infections caused the vessels to leak and expose the tumor cells to the virus. In these experiments, the virus managed to infect and destroy only a small proportion of tumor cells directly, the researchers found, but within five days of the initial infection, the rest of the tumor began to be killed by a powerful immune reaction. Live human trials have commenced in 2018 and the “patient 1” is a pancreatic NET patient. Read more here. Interestingly they added Keytruda (an immunotherapy) to the mix. It’s only been four months since ‘Patient 1’ (Tamara) began the trial, but a mid-treatment CT scan was said to be “promising”. I will keep this article live and bring you updates as I receive them.
Clearly it’s still early days in the Oncolytic Virus field with minimum breakthrough in terms of success on humans. In terms of the Neuroendocrine connection, it is exciting that two programmes are showing results (albeit in mice). We wait to hear from Uppsala on how the human test of AdVince is coming along. My agents are scanning the internet every day looking for any comment.
If you want to learn more about Oncolytic Viruses in general – there’s a great summary here.
Thanks for reading
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