Using HSV-1 to cure metastatic melanoma

Posted by ERV on April 7, 2010
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Metastatic melanoma is definately one of the Cancers That Suck.

We basically have the same treatment options in 2010 as they had back in 1975… and not because we have chemotherapy/immunotherapy that works super great, no reason to change it. Our treatment options just suck, with horrible consequences– Say you have 100 friends that are diagnosed with Stage IV metastatic melanoma today. One year from today, only about 25, 26 of those friends will still be alive.

~25.

Out of 100.

Survive one year after diagnosis.

Maybe fewer (this paper Im reading says 25.5%, Wikipedia says 9-15%).

Melanomas expression of ERV proteins might help us develop new therapies/vaccines in the future, but weve got a vaccine available right now that, apparently, cures some Stage IV metastatic melanoma!

Phase II Clinical Trial of a Granulocyte-Macrophage Colony-Stimulating Factor-Encoding, Second-Generation Oncolytic Herpesvirus in Patients With Unresectable Metastatic Melanoma


They had a study group of 50 people, Stage III to Stage IV (most were Stage IV)… 13 people were cured. “NED”– No Evidence of Disease.

Statistically, they should have been dead within the year.

How did they do this???

A modified Herpes Simplex Virus-1. Regular ol HSV-1 that we are basically all infected with, causes cold-sores in some people? Yeah, scientists gutted out some bits of it (keep it from going into neurons, make it need something cancers make lots of), added immune-stimulating bits (a chemical messenger that REALLY pisses off macrophages).

This modified virus was injected directly into melanoma lesions every two weeks for up to 48 weeks (24 doses). Now, remember these patients were metastatic– yes, they had ‘skin cancer’, but that cancer had spread, to the liver/lungs/anywhere.

Even though the virus was injected into the ‘skin cancer’, the liver lesions, the lung lesions– they were all killed too. Scientists aspirated where the lesions used to be, and all there was was necrotic tissue (dead cancer).

Here is an example of one patient:

Patient 703 was diagnosed in November 2004 with a 10-mm ulcerated lesion on her posterior left shoulder, which was followed by regional progression in August 2005. After three cycles of temozolomide, she experienced progression with retroperitoneal adenopathy, at five subcutaneous sites in the left and right shoulder, in the lung, and with indeterminate lesions in the liver. She received the first injection of JS1/34.5-/47-/GM-CSF in February 2006 into one deposit in the left shoulder only. Within 2 months, this became difficult to palpate. At 3 months, the liver lesions became more distinct and numerous on CT. Treatment was continued into the minimally palpable area until 8 months, by which time all lesions had resolved, including in the liver and lung (Figs 1 and 2). Biopsy of the injection site at injection 15 (the final injection) showed necrotic debris and residual ghost cells with extensive lymphocytic infiltration with follicular center formation. This patient remained off all therapy with no evidence of disease 40 months after her first dose of JS1/34.5-/47-/GM-CSF.

HOLY CRAP.

And it doesnt matter if you are already HSV-1 positive, this still worked.

And while 13/50 were apparently cured entirely, the overall 1-year survival percentage popped up from 25.5% (or 9-15% via Wikipedia) to 58% (58 of your 100 friends with metastatic melanoma are alive next year instead of 25), and 40% in the group with Really Really Bad Metastatic Melanoma.

WHY AM I JUST NOW FINDING OUT ABOUT THIS???

The immunology behind this vaccine for interested parties:

Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma.

Nature paper from 2003 describing the modified HSV-1:

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

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Comments

  1. #1 Jared
    April 7, 2010

    The idea of modifying a virus to specifically target tumors has been around for some time now. Back in the 60′s, they tried just using the wild-type virus strains. Modern genetic tools made this a much more attractive idea.

  2. #2 Texas Reader
    April 7, 2010

    What’s a reasonable estimate of time before this is available to everyone? thanks.

  3. #3 Optimus Primate
    April 7, 2010

    Yay! The last two papers are free to download. :)

  4. #4 ERV
    April 7, 2010

    Texas– I KNOW RIGHT???

    Cause, I mean, it didnt just work on the melanoma. It worked on the liver/lung/pancreatic/etc lesions caused by the metastatic melanoma, so like, would this work for other cancers too?? I think they were just focusing on the melanoma cause they could easily, directly, administer the vaccine. But, CRAP!

    Optimus– Yeah, but theyre really dense. The immunology one was even too much for me (way too impatient to read it well enough to blog on it)– the medical one I based this post on was a much easier read for the general public, and of course, its behind a wall *rolleyes*

  5. #5 Cain
    April 7, 2010

    What are residual ghost cells?

  6. #6 Cain
    April 7, 2010

    NVM found the answer here.

    http://www.justfuckinggoogleit.com/

  7. #7 D. C. Sessions
    April 7, 2010

    What’s a reasonable estimate of time before this is available to everyone? thanks.

    If you’re not yet old enough to vote, it may happen before your children retire. Alternately, you could go to a clinic in Tijuana where they’ll inject you with something that they claim is this modified HSV, but with added woo — and which actually turns out to be something else entirely.

  8. #8 Optimus Primate
    April 7, 2010

    Yeah, but theyre really dense

    Hey-Zeus, you weren’t kidding, were you? I barely made it to the end of the first paragraph before I was like, ” I can has glossary, pls?”

  9. #9 Moron
    April 7, 2010

    > Yeah, but theyre really dense

    Who could dispute the fact that many will gladly “muddy their waters to make them look deep.” Papers from days of yore when it was easier to become a PI — 1960s, early 70s — certainly tended to address simpler hypotheses than the ones examined today. And that’s a big part of why they are so readable. But there was also much less obfuscation.

  10. #10 ERV
    April 7, 2010

    Moron– Who could dispute the fact that many will gladly “muddy their waters to make them look deep.”
    Um, its actually pretty standard immunology, its just information dense.

  11. #11 Birger Johansson
    April 7, 2010

    Cannot activists force the release of the virus strain for “compassionate use”, like HIV/aids activists demanded the early release of anti-retrovirals before they had made it through the lenghty drug approval process?

    I lost my father to this particular cancer, so I understand the frustration of cancer patients and their families.

    BTW, did not ordinary salmonella bacteria turn out to be effective killers of some cancers? Since salmonella is a perfectly survivable disease, there should not have to be a lenghty approval process (according to Wikipedia, only one in 4500 dies of Salmonella enteritidis, which is close enough to “zero” for anyone suffering from cancer).

  12. #12 NP
    April 7, 2010

    Texas reader:
    The vaccine is currently in phase III trials, and they should have results on how many patients respond to treatment by mid-2011. Survival data will probably be available a little later, but I presume they could begin filing for FDA approval with evidence of a good response rate. So my guess would be mid to late 2012, IF the phase III trial is positive – and I must stress this given that many recent phase III trials for melanoma have failed.

    The phase II data is promising, but it is from an uncontrolled trial. Comparing the 58% survival rate with historical controls isn’t always accurate, since trials tend to enrol patients who have a better prognosis to begin with, or some other unexplained factors could contribute to the observed survival rates.

    Case in point: a phase II study for an investigational drug called elesclomol showed a 49% one-year survival rate. However, a large phase III study had to be stopped early because they found that more patients in the experimental arm died than in the control arm. So no matter how promising the preliminary data looks, there’s a sound reason why larger trials are necessary to confirm the findings.

  13. #13 Jesse
    April 7, 2010

    @8 Yeah, one thing that I’ve found is that medical and biological sciences have more jargon than just about any other field. They fascinate me, but having sat in and listened to people flinging the jargon around, I know that my eyes tend to glaze over like a donut. A Krispy Kreme to be exact. I can try fighting back with my own, but their arsenal is just so big. Funny thing is, I should have a job in a medical research facility within the next month or two. I think I should find an applicable dictionary.

  14. #14 Moron
    April 7, 2010

    Try the cancerweb medical dictionary on the web (free). Way quicker than a physical book.

    Theoretically, with the speed of online resources (including searching), the current young generation should be able to produce scholars more profusely educated than have ever existed so far.

  15. #15 Timo Ahopelto
    April 7, 2010

    The oncolytic virus therapy as a new potential treatment strategy in cancer can have its firs break-through this yeaar. There are a lot of signs: trials by BioVex, Jennerex, Oncos, Oncolytics Biotech… And BioVex as the lead is expected to publish strong phase III data this year. i actually wrote a small post on Q1/2010 in oncolytic viruses, check http://oncolyticvirus.wordpress.com

  16. #16 Jesse
    April 8, 2010

    @14 Except the amount of useless information on the web seems to be increasing faster than useful information. It turns into this gigantic time sink where the young generations end up learning a whole lotta useless shit. Besides, a lot of people really suck at google.

  17. #17 Kemanorel
    April 8, 2010

    *gawks and is rendered blind, deaf, and dumb by the sheer awesomeness*

    *tries to think of something to say, but can do nothing but wonder why the fuck stuff like this isn’t getting billions of dollars in research money to get this stuff available to the general public ASAP*

    *drools as he ponders the applications*

  18. #18 Reynold
    April 8, 2010

    Kemanorel: Exactly. This, by damn, is science! If this passes the Phase III trials, this should bump off whatever the hell the MSM is passing for news.

  19. #19 Kemanorel
    April 9, 2010

    Kemanorel: Exactly. This, by damn, is science! If this passes the Phase III trials, this should bump off whatever the hell the MSM is passing for news.

    This should bump ANYTHING ANYONE ANYWHERE is passing for news…

  20. #20 The Chimp's Raging Id
    April 10, 2010

    I know I’m a bit late getting here but feel compelled to say this is definitely worthy of a w00t or two

  21. #21 Prometheus
    May 3, 2010

    *update*

    For those of a fellow follow-the-money bent

    Holy Crap!

    Biovex has the sexiest “We don’t guess wrong….ever!*” bio-tech venture-capital profile I’ve seen in ages.

    They have over 70 million in capital, have been playing big time for less that five years and have built a full size U.S. production facility….while still a private research company.

    They have divided their labs along national regulatory and funding lines and while they are starting Phase III on Oncovex here, they have the NHS go-ahead and started Phase I on ImmunovexHSV2 February in England.

    Somebody knows something, the SEC filings on stock holdings and salaries is phenomenal. I want to know who will be brokering the freekin IPO.

    *I’m talking about the Chang Family. Whenever you run across a futuristic skyscraper or glass space-city on Google image search and you click on it to see which architect was fantasizing, only to discover it is real, in mainland China and fully populated with mysterious bazillionaires….yea, the Changs built it.