New weapon in the pipeline: GMO herpes vs Ovarian and Breast Cancer (+ metastasis!)

This is one of the cool ideas not included in the 1800 human gene therapy trials because its still in animal models, not humans:

Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus

If Ive said it once, Ive said it 1000 times: 'Cancer' is not a monolithic entity. We have not 'cured cancer' because there are lots and lots and lots of different kinds of cancers.

Some ovarian cancers and some breast cancers have a protein upregulated, HER-2. Scientists have capitalized on this observation to create anti-tumor drugs that focus on HER-2, to generate vaccines that teach our immune system to fight HER-2, and have generated pharmaceutical anti-HER-2 antibodies that can be used therapeutically.

The folks in this paper took that observation in a different, but similar direction. You know how viruses need something on their outsides to interact with host cells, so they can initiate infection? Like, HIV-1 has Env?  Well this group of scientists genetically modified HSV-1 to have a different receptor protein-- one that included an anti-HER-2 antibody.

In other words, they slapped an anti-cancer antibody onto a virus, to help make the virus target cancer, and unable to target either its natural cellular target, or healthy tissue. HSV infects the tumor and blows it up. This isnt a far-out-there idea-- Scientists are lovin GMOing HSV-1!

  1. Their GMO HSV could kill HER-2+ cells in tissue culture.
  2. It could kill cells that anti-HER-2 drugs had no effect on.
  3. When they injected mice with human HER-2 cancers (ovarian), the mice that also received GMO virus lived over four times longer (normal mouse life-spans).
  4. GMO virus reduced the tumor burden in mice 95% (ovarian line).
  5. They didnt have as much luck with the breast cancer line-- It doesnt look like any of the mice lived a normal mouse life-span, and they say only 20% of the mice were 'long-term survivors'.

Something to remember, here, is that we arent only talking about big tumors.  The big masses I dont think are the big problem-- surgeons can just cut those out.  No, the problem with cancers, and especially ovarian and breast cancers, are the cancer cells that escape the main tumor and set up shop in the lungs, the brain, the lymph nodes, etc.  But the best part about viruses, is that they can go anywhere that the loose cancer cells can go...

... Can GMO HSV-1 not only kill major ovarian and breast tumors, but also sweep up the metastases?

Kinda! Sometimes!

With the breast-cancer model, spread to the ovaries was greatly reduced in the mice that got GMO-HSV.  Brain metastasis was reduced, but not as impressively.  And, lung metastasis didnt change at all.

So... Yay!... Kinda!... If it works, this will be a new therapy that could 1) treat the main ovarian/breast tumors, 2) will work even if the tumor is resistant to anti-tumor drugs, and 3) can prevent some kinds of metastases!

Ill still take this as a win!

And hope it translates to results in humans :-/

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Unfortunately, Her2 expressed by cancer cells is not normally mutated, so a virus targeting Her2 is also going to hit the non-cancer cells that express this receptor. This is a problem when the virus also "blows up" your heart. I know of at least one Her2 targeted cytoxic therapy that failed in this manner. Secondly, cancer cells also evolve at an alarming rate (not as fast as a virus, but GMO-HSV is not mutating at all as it doesn't even have a polymerase unless something went very wrong) and applying this selective pressure will probably change the dominant clone. Even the best Her2 targeted therapies all eventually develop resistance.

By Dr. Strangelove (not verified) on 07 Feb 2013 #permalink

Utterly pent subject material, Really enjoyed looking through.

By TyffanySweet (not verified) on 11 Feb 2013 #permalink