Sorry if this has been posted before, seems like a pretty cool idea
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what is the exact definition of “functional cure?”
btw, I appreciate the repost as I did not see the other post. thank you!
Hi @Jb007,
Yes, there are a few companies looking at similar strategies (from Hepatitis B Foundation: Drug Watch):
@catcher.007, an in-depth explanation of what functional cure means is in video form here: What do we mean by Hepatitis B cure? - HBV Cure FAQs
Cheers,
Thomas
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Dr. Tu,
thank you so much!
I did not know that we now have different cure level terminologies!
and wow we have so many drugs!
it sure would be nice if we can get one drug to work.
wouldn’t it be faster and effective to have a fewer drugs being worked on instead of so many? It’s like putting fundings and efforts in a few rather than spreading out the fundings and efforts in multiple drugs.
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We don’t know which of these are likely to work, so testing a broad range of approaches is the most efficient way at the moment so that we can get closer to a cure. Once a few look promising then they are pushed along from phase I to II and beyond.
TT
I just found this news in the internet and i think this is another hope to cure HBV. You can read article and watch the interview with Carter Keller.
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Previously discussed here: GIGA-2339 polyclonal antibody treatment
it’s an interesting approach for sure though!
Let’s hope for the best!
Hi @garry5,
It sounds interesting as many of these trials have. Manufacturers give a lot of hype on the initial results before clinical trials where they get real results. I tend to temper my hope in cases like this, since the actual process is now beginning. Most developments fail at this phase. With that said, I think it will be great if it works and can lead to a cure. The more options we have the better it is for everyone.
Thanks for sharing. Bansah1
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From the article: “GIGA-2339 aims to address this gap by using more than 1000 anti-HBV antibodies, replicated from the natural immune response of vaccinated donors.”
One thing that comes to mind is that I’m of the understanding that antibodies from vaccinated people differ significantly to those who develop them due to natural immunity (ie acquiring them from clearing the virus). This is an assumption partly based on prior reading where I saw that hematopoietic stem cell transplants cure chronic HBV but only when the donor has recently acquired then cleared HBV in case studies. Basically it seems that the stem cells start to grow in the recipients liver and produce the antibodies that they learnt from the donor’s environment
I guess it’s harder to get blood samples from that population though. And maybe this will work
Perhaps @availlant could shed some light on this approach? You’re usually great at killing any hope I get 
but for good reason (and thank you for your work)
Thanks @Bob for your comments, these are appreciated.
So the problem in achieving functional cure is two fold:
- We have to remove cells in the liver containing integrated HBV DNA. This is because these cells produce most of the HBsAg in chronic HBV infection (in the form of subviral particles) which continue to suppress the immune response.
- These cells will harbour integrated HBV DNA with lots of mutations (as a result of the genetic diversity in HBV infection).
The development of GIGA-2339 is a recognition of the second problem (a genetically and immunologically diverse pool of HBsAg in chronic HBV infection). However, the problem with GIGA-2339 is that the introduction of a very diverse pool of HBsAg reactive antibodies (these will be the antibodies harvested from vaccinated donors) will do nothing directly to target the cccDNA inside cells (which produces new infectious virus) and more importantly, will not result in the removal of cells in the liver containing integrated HBV DNA. Additionally, antibodies only last for about 21 days in the body. To target those liver cells with integrated HBV DNA, we need a broadly HBsAg reactive population of T-cells (which can remove these liver cells).
Interestingly, the introduction of foreign HBsAg antibodies (with a more narrow spectrum of reactivity) is capable of non-specifically stimulating the innate immune response (we have seen this with VIR-4334 - but this is incorrectly called a “vaccinal” effect). This effect can have some impact on cccDNA activity and lowering HBsAg levels but not enough to achieve functional cure. We may observe this effect with GIGA-2339 when it enters trials in infected persons.
Hi all,
Just consolidating all the discussion on this therapy here. Please be sure to search to see if there’s already an existing thread that would be most suitable for discussions, rather than starting a new thread.
Cheers,
Thomas
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maybe a naive question. Do liver cells have lifecycle that each cell will die and new cell will grow ? if we can prevent infection of new cells, then will virus and its biomarkers gone with the death of old liver cells ?
There’s a good overview of that here: Example entry: Hepatitis B cccDNA viral reservoirs - stubborn nails in the quest for a complete cure - #14 by DBuddha
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