Dendritic cells in cancer treatment

[wasteofo2]

http://www.foxnews.com/story/0,2933,104730,00.html

The video is more informative than the article.

 

[Monique]

[?] I don't get it.

In short: researchers isolate dendritic cells (the master immune cells) from a cancer patients' blood. They expose these immune cells to a mixture of inactivated cold virus and p53. These immune cells then learn that p53 belongs to a pathogen and should be attacked when encountered.

These activated cells are then injected back in the patient, and the own immune system will attack any cell expressing p53.

Now: what I don't get: p53 is the good guy!

p53 is a tumor surpressor gene, a transcription factor that causes a cell to arrest its cell cycle in G1 or 2 or to perform apoptosis.

The trigger for p53 expression is dna damage or oncogene activation (among other things) and p53 is always present in low amounts in cells in an inactive form, ready to become activated in the case something goes wrong.

I would expect for p53 expression to be high in cancer cells (the protein probably has mutations so that it doesn't work properly) but it is also present in normal cells.

I DID hear that it only works in few cancers, apparently only in the ones where p53 cannot be activated by the cell due to mutations? That would explain, since the good guy in that case wouldn't be a good guy anymore if it has lost its function..

 

[wasteofo2]

So, aside from fighting the cancer, it'll fight all your cells in general?
Sounds like a good biological weapon, train your immune system to attack a substance in every cell in your body...

 

[Monique]

Well, the thing is that it normally is present in low concentrations and it is inactive, in the cancerous cell the molecule would be active and thus have a different conformation. I am not sure if the immune cell is only specific to the activated form, and whether a mutant p53 can become activated at all..

The concentrations might be higher too in a cancerous cell, and probably in such a cancerous cell the p53 is directed towards the plasma membrane, where it gets exposed to the outside so that the immune cell is able to recognize it. A normal cell probably has no p53 exposed to the outside of its membrane.

As I said, I don't get it :P

How do you envision it being applied as a biological weapon? I really don't think that is feasible in this manner :) there are much easier ways to attack every cell in someones body by using conventional methods like microorganisms or toxins, nothing new under the sun.

 

[Monique]

There is a different method based on gene therapy that targets the same gene, in development by Chinese researchers !

http://www.newscientist.com/news/news.jsp?id=ns99994420

The treatment consists of an adenovirus designed to insert a gene called p53. This gene codes for a protein that triggers cell suicide when cells start to run amok, preventing them becoming cancerous.

Many tumours arise after the mutation or inactivation of p53, and in cancers of this type restoring the protein should kill the tumour cells. This approach has already been tried in the US, with mixed results.

The problem is that they use an adenovirus, which is immunogenic: patients' immune respons can react very fiercely when a wrong dose is given for instance. The other problem with this virus is that the expression of the gene is only transient.

 

[wasteofo2]

Originally posted by Monique

How do you envision it being applied as a biological weapon? I really don't think that is feasible in this manner :) there are much easier ways to attack every cell in someones body by using conventional methods like microorganisms or toxins, nothing new under the sun.

You're right, plenty of efficient biological warfare means to kill people. I just envisioned training a dendritic cell to attack something which is found everywhere, or maybe just in your brain or liver or something. Then, making a virus which will cause your dendritic cells to act that way.