HIV virus used to turn white blood cells into cancer serial killers | Hacker News Reader

HIV virus used to turn white blood cells into cancer serial killers

geek.com

112 pointsukdm35 comments

To clarify, the modified HIV virus in this case was used as a vector to deliver an antibody specific to the cancer onto a T-cell. The T-cell then goes on to destroy the cancer. HIV is one of the most efficient vectors for genes.

http://en.wikipedia.org/wiki/Viral_vector

http://en.wikipedia.org/wiki/Lentivirus

http://en.wikipedia.org/wiki/Chimeric_antigen_receptor

http://www.nejm.org/doi/full/10.1056/NEJMoa1103849

EDIT: Also note that the HIV vector is used to modify the T-cell before it is inserted into the human. The HIV is never actually inserted into the human (in this case).

Such viral vectors are routinely used in the lab to knock in a variety of genes in the cell. Vector is really the packaging. What was important in the study was the actual antigen which has packaged in the vector.

Without a doubt. I was only commenting on the HIV vector because there are so many that say, "What the hell?" when they hear "HIV."

I know I did, until I read further into the article.

This is incredibly good news. So many researchers have been looking for a way to alter the inmmune system to target cancer, and it's surprising (but also makes sense) that the solution seems to be around HIV. It's this kind of out of the box thinking that pushes forward.

And this: "this small trial involving just three patients was lucky to go ahead at all. The study was rejected by pharamceutical companies and the National Cancer Institute.".

There's a very good talk on TEDMed from David Agus, about proteomics and cancer research. He bubbles up a similar concern about limitations of clinical trials.

http://www.ted.com/talks/david_agus_a_new_strategy_in_the_wa...

His graph with heart disease, etc. is misleading; if we have made all those reductions in those areas and cancer deaths have remained the same, we have obviously made progress in cancer as well: since less people are dying of the other stuff, they have a greater chance of eventually contracting cancer.

I agree you could argue that. But rather than crunching numbers, I think his point was to illustrate the state of some cancer treatments today. How despite of everything and all advances in medicine,we still need to make HUGE improvements in cancer.

For example, pancreatic cancer. Prognosis is 20% 1 year survival and five-year rate is 4%. The best approved treatment so far is Gemzar, which was introduced in the early 80's. It's improve rate over other chemos was that it works in 23% of the patients, and improves the median survival to 5.65 months compared to 4.41 months with 5-flu chemo.

Over 20 years and some of the best we got is +1.2 months and for only 23% of the patients. That's what he's pushing for and I support,improving this rates.

In the end It's not about crunching numbers and making one disease or other look better tackled. It's about having hope for all this people and know something can be done, instead of staring at such a grim prognosis.

It's awesome to see one shitty thing in life being used to get rid of another shitty thing in life.

gold.

More comments here http://news.ycombinator.com/item?id=2873604

This is very exciting. Anyone have any thoughts on the extensibility of this to treating other cancers?

The main issue is that for this to work, you need to know specifically what antigen you're targeting on the tumor cells. Think of the antigen as a unique tag that the immune system can use to differentiate cells (a "natural key" if you will). In the majority of cancers we haven't got a clue as to what we should use as for an antigen (though it's not an insurmountable probelem). However, with leukemia they can use CD-19 which is found exclusively on the surface of normal and cancerous B-cells. The last thing you want is an antigen that "looks" like something common, so CD-19 apparently fits the bill there as well. If you choose something non-specific, then the immune system can go after all kinds of other tissue that you don't want it to which could very likely kill the patient.

All that being said, targeted therapy like this is probably the future of cancer treatment, but it's going to take tremendous effort to work out all the kinks. The immune system is ferociously complex, and is still poorly understood. However, it does have the advantage of being battle tested throughout evolution.

Thanks for the reply. Just while you're here, I was wondering if I could ask another question. Am I right in thinking that they used the HIV virus to 'program' the white blood cells? And if so, in the future might it be possible to reprogram the cancer cells themselves? Perhaps the virus could 'patch' the broken/missing DNA?

As you can tell, I'm horrifically ignorant on the topic but I would be grateful if you could indulge me :)

While it may be possible in theory to patch/fix the cancer cells, you'd need a virus that can target them specifically. In the case of using HIV here, it's because it's so efficient at getting into the immune system that it can be used as a vector to reprogram it. I've got to imagine that other "super viruses" could be used in a similar manner if they also target things so well.

simcop2387 is right in that the biology here gives them a leg-up on what would otherwise be an even more difficult problem. The whole class of lentiviruses (of which HIV is part) are useful for delivering genes to target cells. In this case, HIV is very good at finding T-cells which are exactly what whas needed here to trigger the immune response.

You are correct that they are using the HIV virus to reprogram the T-cells. They basically are making them express a very specific protein on their surface which allows them to seek out the tumor cells. When they find one, that protein is "wired up" to the cells' ordinary immune system genes that do their thing as they normally would.

Basically, the T-cell is like a hit man. It shows up, punches a bunch of holes in the target cell's membrane. Then it dumps a bunch of enzymes in there that go in and break important stuff. Once the chaos reaches a certain point, the target cell decides all is lost and it pushes the big, red "self destruct" button and goes through programmed cell death (apoptosis).

The actual work to make the viral vector and test it in mice was published in a study in 2009, so this new article is news because it's the follow-up where things were done in humans the first time (and they actually worked). From looking over the literature, apparently people have been trying this for some time but it has been failing for one reason or another.

> has been experimenting with using a harmless version of the HIV virus

I wasn't aware such a thing exists. Anyone care to elaborate? Is it harmless or probably harmless?

It's certainly more harmless than most types of cancer.

It's very harmless. Obviously there's a good number more technical details in here, but the gist of it is we take the parts of the HIV virus that makes it so good at proliferating, take out the genetic material that makes it harmful to our cells, and put in our own genetic information for the HIV-derived virus to inject into our target cells (known as a viral vector).

Contrary to the mental connotation, it's a very harmless procedure that's often used even in BSL-2 labs. It's not to say that there aren't risks involved, but chances are you're not going to end up with AIDs.

HIV-derived lentiviruses have been in use for a long time now and are a proven research tool. Coincidentally I just grew and harvested a new batch of lentiviruses this past Tuesday to treat cancer cells with shRNA.

Nothing in life is without risk, and using HIV is no exception. However, in comparison to the risk of dying from leukemia, I think it is fair trade-off.

More details: http://www.vcu.edu/oehs/chemical/biosafe/lentiviralvectors.p...

In general, a virus consists of some genetic material and some method of getting that genetic material into a cell. You can swap out the virus's own genetic material for the genetic material of your choosing, and the delivery mechanism will still work. If you use HIV's "delivery system" to deliver genetic material that encodes a cancer-fighting protein, then you get cancer-fighting T-cells (a type of immune cell), since HIV targets T-cells.

This is a massive oversimplification, of course. But anyway, the harmlessness of the viral vector depends on how efficiently you can separate the virus's delivery mechanism from its own infections genetic material.

The results of this sound amazing, but the article is frustratingly vague about what role the HIV virus plays. The interviews in the video don't mention it at all. I think most people will assume the patient is being infected with some variation of the virus, which seems rather scary, but it doesn't sound like that's the case.

Since the emphasis is on genetically modifying white blood cells and injecting them back into the patient, which doesn't seem to need a virus as a delivery mechanism, I'm guessing the HIV's role is somewhere in the genetic modification?

From what I've seen in other places what was done is, they took some of the patients T-Cells, and altered them. They did this by taking the RNA out of some HIVs and replaced it instead with a sequence to look for a specific antigen on the cancer cells. Then they took the HIVs and introduced them to the T-Cells and let them get infected. Since the original nasty RNA wasn't present, it won't replicate, but it will make some T-Cells that target the antigen on the cancer cells. After reintroducing to the patient, their immune systems then pick up from other signals that we don't full understand that some T-Cells are attacking this antigen, so it should make more of them.

I'm the first to notice (or care)... "HIV virus"? Department of Redundancy Department?

Like GPS System? The acronym takes on a life of it's own as a 'word'.

Is GPS System common? That looks and sounds weird to me.

Sure, I've heard it said more than seen it written. Especially on news stories: "the car was tracked using the GPS system", etc.

To most people, HIV is a disease. What's the more elegant alternative?

I hear a lot of people call it "The HI virus".

The most acceptable way may not be the most correct, but to correct it is more effort than it's worth.

http://en.wikipedia.org/wiki/RAS_Syndrome

Also discussed at great length over here:

http://news.ycombinator.com/item?id=2873604

This is a good example of the same story, not cross-connected, getting split discussions.

I love the idea of disarming one virus and brainwashing it to kill another. I wonder how long it is before cancer is eradicated.

Forever: cancers are not eradicable unless evolution and mutation and gene expression from adverse environments and ... are all eradicable.

That's a different thing than assessing if a certain instance of cancer is itself curable in a certain afflicted host. Perhaps it is worth hoping for that.

"Good news, we found a way to treat your cancer."

"Great! What is it?"

"We're going to give you AIDS."

"..."

You didn't read the article, did you?

Reply on news.ycombinator.com