HERVs and Breast Cancer - A marker for what is but should not be

Common everybody! Sing the chorus with me, you know the words!

The vast, vast majority of ERVs are junk. They are genomic pirates, and your genome is doing the best it can to keep them silent. When ERVs are making noise, its a sign that something has gone wrong. Very, very wrong. Like, for example, breast cancer:

Immunotherapeutic Potential of Anti-Human Endogenous Retrovirus-K Envelope Protein Antibodies in Targeting Breast Tumors.

This paper has the potential to lead to something incredible. Lemme try to convey how cool this is...

Like I always say, cells not only making ERV RNA, but actually generating ERV proteins is almost universally a VERY bad thing. Of course the proteins themselves can cause trouble, genomic instability and cytotoxicity mayhem and such, but because your genome does try so hard to keep these guys quiet, if the ERV proteins are getting out, it means the epigenetic profile of the cells is in chaos. Anything can go wrong from there. Any gene can be disregulated and cause trouble, independent of the ERVs specifically.

This lab found that malignant breast cancer cell lines express a full length, glycosylated HERV-K Envelope on their cell surface, while nonmalignant breast epithelial cell lines and our friends 293Ts do not.

So, this HERV-K Env might be a putative marker for breast tumors.

... Now what? What are we supposed to do with this information?

These folks generated a collection of monoclonal (single antibody variants that recognize a protein, not a collection of variants that recognize the same protein, called polyclonal) antibodies that recognize this HERV-K Env.

Now, just because an antibody recognizes a protein, it does not mean that the antibody will perform the trick you want. Think of it this way-- not every anti-HIV antibody can neutralize HIV, and not every anti-tumor antibody can induce apoptosis or convince immune cells to kill the tumor. (for the lab folk out there-- not every antibody that works perfectly in an IP works for Western Blots or immunohistochemistry.) So this group took their collection of anti-HERV-K antibodies, and asked which one performed the trick they were interested in-- stopping breast tumors.

They found that one of their antibodies, H6, could not only inhibit the growth of breast cancer cell lines, but it actually induced apoptosis on its own. Traditionally, we would think that an antibody would need the help of other immune cells to kill a tumor, but this guy was convincing the tumors to kill themselves all on its own.

This was all done in a tissue culture dish, and 'cures for cancer' in vitro are a dime a dozen (literally. like, bleach does the trick).

So this group moved to an animal model-- What if they put these laboratory human breast tumors into mice, and then treated the mice with the antibody? The antibody couldnt take its time snuggling up to the cells-- it would have to fight with physiology, a real world environment. H6 treated mice had tumors a third of the size of the mice treated with a non-specific antibody.

But H6 couldnt clear the tumors on its own. The tumors were smaller, but they were still there. This is really too bad, as since HERV Env is only present on the surface of Wrong cells, there are probably minimal side-effects vs the hell people go through with chemo/radiation. So if we started giving people this antibody as an anti-breast cancer drug, we would have to give patients traditional therapies too. But, this would be another angle to attack the tumor. Help us make sure every damn one of the cancer cells are dead.

And, because these HERVs are junk and expression of these proteins is a Very Bad Thing... knowing this HERV-K Env is on the surface of some tumors might mean that we could theoretically vaccinate people for any form of cancer where HERV-K is a marker! ... Oooor maybe we could just keep the HERV-K Env antibody as an external therapy. Syncytin is a HERV-W, but we might want to avoid any potential cross-reactivity that would lead to Moms attacking their placentas...

... Anyway, now we get to another kicker. Yeah, this approach works in cell lines in tissue culture flasks and in mice. But theyre cell lines in artificial conditions. What about real human breast tumors?

They looked at 223 breast tumors. This HERV-K Env was found on the surface of 148 (66.4%).

Of the ones that were HERV-K positive, 43% were metastatic (the cancer is spreading, VERY bad). Of the HERV-K negative breast tumors, only 23% were metastatic.

HERV-K positive breast tumors are more likely to be REALLY BAD breast tumors.

Anti-HERV-K Env antibodies might be a fantastic new weapon in our arsenal against some really bad tumors. We wont know until we get into clinical trials, but this group is at MD Anderson Cancer Center, so Im sure this is moving down the pipeline.