Thoughts on virus based cancer therapy?

[Sheldor]

Came across this company called Genelux thats working on some seemingly novel cancer treatments and was curious what everyone thinks.

I've attached a PDF of one of the Nature articles referenced on the companies website. It seems promising, but I'd be interested to see what everyone has heard at conferences/etc. about the promise of these new techniques.

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[Gfunk6]

This has been on-going since at least the mid-1990s if not earlier. Sounded good then and it sounds good now but show me some clinical data beyond a Phase I or early Phase II clinical trial.

Until then, it will remain but a good concept.

 

[hot sauce]

Completely agree with gfunk. It sounds awesome but going from the test tube or even a nude mouse to a viable therapy is a huge leap. There are a number of groups looking at similar therapies and it may happen someday but I wouldn't be rushing to invest in genelux either.

 

[Trojan1990]

Agree. Mice are one thing but in human data from trials are another. Thankfully, Genelux has been very successful in Phase 1 trials at Royal Marsden Hospital in London and have completed patient selection in Germany for trials there. US trials were approved last summer by the FDA and will begin at UCSD (Head and Neck) and Sloan Kettering (Mesothelioma) within the next 2-3 months. To date, the company has shown an ability to treat 44 lines of cancer. 9 Patients from the Marsden trial are considered disease stable with up to 6 additional patients that may be included in that category. Additioanally, another trial is being planned to treat a broader spectrum of cancers at a third location. You can find the two active trials on the Clinicaltrials.gov site by searching the company name. The true genius of this is that the vacinea does not integrate with the dna of the cancer cell so there is no mutation. It is also large enough to carry multiple payloads to the tumor directly. Combined therapy with drugs like Avastin and Chemo have shown to have a very synergistic effect.

 

[Charles_Carmichael]

This has been on-going since at least the mid-1990s if not earlier. Sounded good then and it sounds good now but show me some clinical data beyond a Phase I or early Phase II clinical trial.

Until then, it will remain but a good concept.

+1. Completely agree with this sentiment.

Agree. Mice are one thing but in human data from trials are another. Thankfully, Genelux has been very successful in Phase 1 trials at Royal Marsden Hospital in London and have completed patient selection in Germany for trials there. US trials were approved last summer by the FDA and will begin at UCSD (Head and Neck) and Sloan Kettering (Mesothelioma) within the next 2-3 months. To date, the company has shown an ability to treat 44 lines of cancer. 9 Patients from the Marsden trial are considered disease stable with up to 6 additional patients that may be included in that category. Additioanally, another trial is being planned to treat a broader spectrum of cancers at a third location. You can find the two active trials on the Clinicaltrials.gov site by searching the company name. The true genius of this is that the vacinea does not integrate with the dna of the cancer cell so there is no mutation. It is also large enough to carry multiple payloads to the tumor directly. Combined therapy with drugs like Avastin and Chemo have shown to have a very synergistic effect.

That's great, but let's see how it fares in phase II and phase III trials (if it makes it that far). It's a cool idea, but so far, hasn't really worked out as expected in humans.

 

[Gfunk6]

Here's an interesting news article about a novel antibody used by Stanford researchers to treat cancer in preclinical models. It was published in PNAS.

 

[hot sauce]

Agree. Mice are one thing but in human data from trials are another. Thankfully, Genelux has been very successful in Phase 1 trials at Royal Marsden Hospital in London and have completed patient selection in Germany for trials there. US trials were approved last summer by the FDA and will begin at UCSD (Head and Neck) and Sloan Kettering (Mesothelioma) within the next 2-3 months. To date, the company has shown an ability to treat 44 lines of cancer. 9 Patients from the Marsden trial are considered disease stable with up to 6 additional patients that may be included in that category. Additioanally, another trial is being planned to treat a broader spectrum of cancers at a third location. You can find the two active trials on the Clinicaltrials.gov site by searching the company name. The true genius of this is that the vacinea does not integrate with the dna of the cancer cell so there is no mutation. It is also large enough to carry multiple payloads to the tumor directly. Combined therapy with drugs like Avastin and Chemo have shown to have a very synergistic effect.

References please.

 

[Trojan1990]

References please.

You could start by looking at the published ASCO results from Marsden.

http://www.marketwired.com/press-re...ation-2012-asco-annual-meeting-gl-1663303.htm

Dr LAUER from the Tubingen trial has begun publishing data. Most recently at ASCO last June. Look for all four trials to publish data soon. I've seen the science, and you will too soon.

 

[clinonc]

Like most targeted therapies, oncolytic viruses will probably have a bigger impact when used in conjunction with other modalities, like radiation. See this review article from the Marsden group: http://www.ncbi.nlm.nih.gov/pubmed/21704402

 

[clinonc]

There is some preliminary phase III data in melanoma. It's not Earth-shattering. http://www.medscape.com/viewarticle/814740

 

[arthurdent]

Somewhat ironic to be astroturfing as "trojan," no?

 

[BraggPeak]

Somewhat ironic to be astroturfing as "trojan," no?

There was a nejm letter a few months ago about anti cmv therapy and GBM. One hospital in Europe with 2 year survival if 70%, albeit small numbers...still got I to nejm (as letter).

I'm using my phone so can't upload it now, but can later

 

[thesauce]

There was a nejm letter a few months ago about anti cmv therapy and GBM. One hospital in Europe with 2 year survival if 70%, albeit small numbers...still got I to nejm (as letter).

I'm using my phone so can't upload it now, but can later

Here's a couple of letters in neuro onc saying this is old news and not particularly convincing "an underpowered randomized phase II study of valganciclovir
demonstrated lack of efficacy, and yet a biased retrospective analysis subselecting favorable patients gets unwarranted publicity in the NewEngland Journal of Medicine."

 

[Trojan1990]

Somewhat ironic to be astroturfing as "trojan," no?

Wow Artie! Pretty strong statement. I'm not the one who started the thread, but thought I would help shed some light on the subject for those interested. But I guess you know better, huh?

clinonc. One of the articles you site is co-authored by Dr Herrington who is one of the investigators of the GL-ONC1 virus at Royal Marsden. Actual human trials with combination therapy is being conducted by Dr Loren Mell at the UC San Diego Moores Cancer Center on head and neck cancers.

Results have been presented at ASCO in Chicago in the last few years from both Marsden and Tubingen trials. Here is an excerpt of Dr Lauer's findings (in humans):
Abstract Disclosures

2013 ASCO Annual Meeting Proceedings Errata
Abstract:

Background: For therapy-resistant peritoneal carcinomatosis (PC) viruses exhibiting oncolytic properties open up new perspectives. Our phase I/II study in patients with refractory PC (NCT01443260) is designed to assess the safety, MTD, and anti-tumor activity of GL-ONC1, a recombinant vaccinia virus (VACV) genetically engineered to selectively replicate in and destroy cancer cells. Methods: GL-ONC1 was administered intraperitoneally up to 4 times every 28 days under a standard 3+3 dose escalation design. Safety was assessed using CTCAEv4.0. Anti-tumor activity was determined by “fluid biopsies” obtained via repetitive paracenteses and by serial PET-CT scans. Patient samples were collected for pharmacokinetics, pharmacodynamics and viral shedding analysis. Results: Up to now, 4 patients have received 10 doses of GL-ONC1 ranging from 107 to 108 infectious viral particles per application.Adverse events have generally been limited to grade 1/2, being mostly transient flu-like symptoms as well as increased abdominal pain resulting from treatment-induced peritonitis. No DLT was reported. No viral shedding was observed. In one gastric cancer patient, effective intraperitoneal replication of GL-ONC1 was demonstrated for more than 3 weeks. Using either anti-EpCAM or anti-VACV specific antibodies, around 5% of all ascitic cells were found to be EpCAM-positive 3 days after treatment in this patient, and only around 5-10% of these cancer cells were VACV positive at the same time point. In contrast, 4 days later (i.e. 7 days after virotherapeutic treatment), less than 2% of all ascitic cells were still EpCAM-positive, and more than 90% of these cancer cells were VACV positive. Of note, VACV-positive cancer cells morphologically showed significant degenerative changes. Conclusions:Preliminary data demonstrate that GL-ONC1 is well tolerated when infused intraperitoneally. Importantly, a single intraperitoneal delivery of GL-ONC1 was found to be sufficient to cause a dramatic decline in the number of malignant cells in the ascitic fluid, suggesting that GL-ONC1 effectively removes tumor cells in the ascites of patients with PC. Clinical trial information: NCT01443260.


Maybe it's just me, or does a "dramatic decline in the number of malignant cells…" sound like it's working? Watch for something coming out of the Head and Neck ASCO meeting in Scottsdale on Feb 20-22.
http://www.asco.org/meetings

You may want to look into the research being done by Dr. Yuman Fong and colleagues at Memorial Sloan Kettering with the Genelux virus. Along with having chaired the Recombinant DNA Advisory Committee for NIH
http://oba.od.nih.gov/rdna_rac/rac_about.html he is also on Genelux's scientific advisory board. I am inclined to agree with his assessment of the science in terms of the promise of this approach to eradicating cancer. Also see this recent publication:
http://www.eurekalert.org/pub_releases/2014-01/foas-evi013014.php

Findings from studies using the virus have not escaped the mainstream media either:

http://abcnews.go.com/blogs/health/...-may-help-treat-deadly-form-of-breast-cancer/

http://therenodispatch.blogspot.com/2013/07/exclusive-does-san-diego-biotech-firm.html

 

[Trojan1990]

arthurdent

Somewhat ironic to be astroturfing as "trojan," no?

Artie,

In case you are still interested in this type of treatment or you happen to be at ASCO next week:
http://globenewswire.com/news-relea...rapy-GL-ONC1-at-ASCO-Annual-Meeting-2015.html

Interesting in light of Amgen's recent recommended approval of their BioVex virotherapy T-Vec:
http://www.pmlive.com/pharma_news/fda_panel_backs_amgens_t-vec_for_melanoma_725181

Complete Response (CR) and Partial Response (PR) are extremely good from the UC San Diego trial. MSKCC results for Epithelioid Mesothelioma are great as well. I recommend you look up the posters when they become available.

Just sayin'

 

[thaddeus]

"Just sayin'" is apparently synonymous with linking to company press releases.

Actually reading the second link reveals this minor detail:

"Amgen revealed earlier this month that the drug was unable to improve overall survival in the OPTiM trial."

So the FDA might approve a therapy that is unable to improve overall survival in patients with advanced melanoma, a population in which HUGE gains have been shown recently with anti-PD1 therapy. I suspect approximately zero people will ever utilize this treatment even if it does get approved.

Meanwhile, the rest of us will wait for data more convincing than a couple of phase I posters at ASCO before getting too excited about this stuff.

 

[Trojan1990]

Amgen's results are admittedly weak at just 16%. The point of the post was to draw attention to the increased attention and relatively low bar for approval.

So you don't have to read into anything, here is a link to the ASCO site for the abstracts to be presented:

http://meetinglibrary.asco.org/sear...tType:Abstract&body=gl-onc1&meeting_id[0]=156

New multi-day dosing regimen going very well. Will let you know when that data is available for public consumption. Until then, control your excitement.