Immune system! SHUSH! The viruses are trying to get some work done!

Scientists all around the world are creating legions of genetically modified viruses to treat/cure human afflictions, from nicotine addiction to hemophilia (A and B).

One disease a lot of folks are focused on in brain cancer.  Certainly not a monolithic entity-- but scientists are working on viruses against them all.  One of the viruses on the front lines against cancer is herpes.

Good old fashioned cold sore viruses love to blow up brain cancers.

But while HSV-1 has worked well in cell lines and some animal models, human trials have not worked out as well (sigh, sigh).

WHY???

Maybe this is why:

NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors

Its that damn immune system getting in the way.

Not in the way you might think-- Its not anti-HSV antibodies neutralizing the anti-cancer viruses, or anti-HSV cytotoxic T-cells-- It is Natural Killer cells that are preventing HSV-based anti-brain-cancer strategies from reaching their potential.

NK cells are not part of your adaptive immune response-- they are part of the innate immune system.  They are not specific for Virus A or Bacteria B, but instead recognize broad patterns of 'wrongness'.  If they see something that is 'wrong', they kill it.

In this case, the cancer cells, when infected with the anti-cancer HSV, produces a couple 'SOMETHING IS WRONG!!' signals.  So NK cells mosey on up into the brain and kill the cancer cells.

Well, 'YAY!', right?  The NK cells are killing the tumor... and the whole point of this exercise is to kill the tumor... so...

The problem is, the NK cells kill the HSV infected tumor cells before the tumors can produce babby viruses.  If left to its own devices, the HSV would continue to replicate in, infect, and kill the tumor cells until ALL the tumor cells were dead.  Once the tumor is gone, the HSV will functionally 'starve to death'.  No HSV, no cancer.

But the NK cells break the cycle.  It kills the infected tumor before more viruses can be made, so the virus goes 'extinct' before the tumor.  Once the HSV is 'dead', the NK cells leave.  They dont kill the tumor.  No HSV, but the cancer is still there.

So what does this mean for HSV-based anti-cancer therapies?

The scientists in this paper generated mice that lacked the ability to transmit the 'SOMETHING IS WRONG!!!' signal between infected tumors and NK cells, and the mice lived longer, the HSV therapy worked.  But that is an entirely unhelpful approach for humans.

The good news is, they identified at least two reasons for why this therapy hasnt worked as well in humans.  Now we have at least two targets for improving this therapy.  Maybe it will be as simple (hah) as as throwing in some siRNA into your GMO HSV.  Maybe some anti-'SOMETHING IS WRONG!!!' antibodies.  Who knows what solution will end up working the best.  But its a hellovalot easier to solve a problem when you know what the problem is.

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Great stuff! Very cool.

By Mike Olson (not verified) on 26 Nov 2012 #permalink

How likely is it that HSV could be engineered to wipe out other HSV infections?

Really, homeopaths should just love it ;)

By Mike Lewinski (not verified) on 26 Nov 2012 #permalink

Totally off topic, but wanted to thank you: I spent some time answering my kids questions on how vaccines "shots" keep you from getting sick last night. While I have long understood the basic functions of the immune system, having read your descriptions of them in LOLspeak over the past several years really helped me to put the concepts into terms that my boys could understand. So thanks.