Monoclonal Antibodies & Telomerase

[The Thing]

Since monoclonal antibodies can be produced to allow the immune system to target virtually any compound, it can used to target specific compounds unique to cancerous cells. My question is, can it be used to allow the human immune system to target telomerase and to track down, this way, the tumor sites and cancerous cells?

[rakuenso]

Even if it does work, you can say bye bye to stem cells as well as your bone marrow.

[The Thing]

How so?

Stems cells do use telomerase. But how do the "telomerase inhibitor" researches get around the fact that whatever they're making can affect stem cells as well as cancerous cells?

[Dak]

i dont think telomerase is more common in cancer cells -- more that the bodies natural telomerase inhibiter is abscent.

 

hence why something that closes the gap junctions between cells is a carcenogenic -- it stops the cell recieving telomerase inhibitor from neighboring cells.

 

so targeting telomerase wouldnt be that useful, as most cells have it, and cancer cells, afaic, dont have it any more than non-cancer cells.

[Yggdrasil]

Antibodies can only recognize antigens on the surface of cells. Since telomerase is in the nucleus of cells, which is inaccessible to antibodies, anti-telomerase antibodies could not be used to target cancer cells.

 

However, cancer cells do display some unique antigens on their surface which can allow the immune system to target cancerous cells. However, researchers are still trying to identify and study there antigens and develop treatments based on this principle (immunotherapy).

[Dak]

dont killer-t-cells and mast cells do that anyway?

 

or is that killer-t-cells and natural killer cells?

[rakuenso]

How so?

Stems cells do use telomerase. But how do the "telomerase inhibitor" researches get around the fact that whatever they're making can affect stem cells as well as cancerous cells?

 

maybe because its done in vitro?

[Yggdrasil]

Cytotoxic T-cells will generally kill cells exhibiting uncontrolled growth. However, most cancer cells in a tumor have mutations which make them invulnerable, or at least more resistant, to cytotoxic T-cells.

[The Thing]

Is there a way to induce an immune response to telomerase? That way the body's own T-cells can destroy the cancerous cells that are using telomerase to become immortal. Is there a way to do this (i've heard of something called telomerase-peptide). If so, how does this work? Any info is welcome plz.

[The Thing]

Oh btw, are there any experiments around this I can do? I am researching this for a school biotech challenge, and any info or advice is welcome. I am no genius when it comes to biology of this calibre, but plz gimme a hand and advice and any ideas as to any experiments I can do for this project.

[Dak]

thing is, every time chromosomes replicate they shorten. this is countered by telomerase, which extends the telomere of the chromosome in order to combat this shortening.

 

thus, every cell that wants to replicate more than a few (i think its something like 15 times) and survive has to make telomerase, so targetting it wouldnt be too great an idea.

 

to prevent cancer, our cells make a telomerase inhibitor so that, in any cells that rapidly replicate, the telomerase cannot keep up with the rate of telomere depletion and the cell dies. this telomerase inhibitor is shared by cells via gap junctions, so that even a cell that is a bit broke and thus not producing telomerase inhibitor will be cancer-proofed by its neighbours telomerase inhibitor.

 

hence why chemicals that block gap juctions are carcenogenic.

 

soooo... given the prevalance of telomerase, i really wouldnt like to have a telomerase-targeted antibody floating around in my blood.

 

if anything anti-cancerish is to be done re: telomerase, id say it would be an increase in the amount of telomerase inhibitor at cancer sites; maybe a 'highly-active-telomerase-targeted telomerase-inhibitor vector' or something. or possibly a cytotoxin that is active only in the abscence of telomerase-inhibitor (possibly)

 

hmm... i dont suppose that NK cells or cytotoxic-t-cells somehow use the level/activity of telomerase-inhibitor to attract them to cancer sites, do they? i suppose that, if they do, it could, in theory, be used to target tumors.

[zyncod]

It's not a bad idea. You could create a mouse anti-telomerase: human Fc fusion antibody to a telomerase peptide and it could attack cells that are presenting telomerase fragments on MHCI. And attacking telomerase-expressing cells is not really that much of a problem - even with the inhibitors, telomerase is expressed at a low level except in stem cells (and cancers). The stem cells can be easily replaced by saving cd34+ cells from peripheral blood before beginning this procedure.

 

However, this would require years of time and tens of thousands of dollars, so I don't really think it's appropriate for a high school science project. Good idea though.

[rakuenso]

a decent centrifuge alone can cost more than 10,000 dollars

[The Thing]

Hmm, good point.

Do you know any experiments I can conduct around this topic for the project? That is , I may have a university sponsor.

[Helix]

I'm a bit late in the discussion but replying to what was previously said, why use monoclonal antibodies, not proven in the lab to be viably effective, when telomerase inhibitors work just as well? There are side effects (skin toxicity, impotency among others mentioned before) but the option is still "alive." I was under the impression monoclonal antibodies fell out of favor for whatever reasons.

[zyncod]

No, monoclonal antibodies are still in use for some diseases. Like all other treatments, they weren't as useful as people said they were going to be, but they are still of some use. Why use a monoclonal in place of telomerase inhibitors? No reason. Of course, neither of these is actually going to work, as they are fairly simple ideas and would have been tried a decade ago.

[Helix]

Well don't speak so fast, as in all of genetics things aren't as simple as they seem. I am not an expert on either but I do know telomerase/telomere therapies are far from "ineffective." I am currently working on a research project with telomeres and they are, in my view, the most promising aspects of modern genetics.

[Emily]

For tumor immunotherapy, a T cell based response is more effective than B cell. That's why majority research focus on T cell based immunotherapy.

TERT has been tested as the target for tumor immunotherapy; you can find several literatures in recent publications, even human phase I clinical trial.

[Helix]

What Emily said is true, TERT (and specifically hTERT) is being used extensively in anti-cancer vaccines [http://www.geron.com/showpage.asp?code=prodcatv]. And telomeres are also being used to probe why senescence doesn't occur in malignant cancer.

 

I think it's a bit wishful to think the cure to cancer and the secret to aging will be handed to us on a silver platter. Just like in all of biology, there will be hard work involved. Sorry to disappoint.

[The Thing]

Thx for all the replies. It was just a thought that came to me, and I thought I'd discuss it.

Another question I have is how can an immune response be induced towards a substance that is usually considered benign? That is, training the immune system to attack something it wouldn't normally attack? Can we control this?

[rakuenso]

Look up the mechanisms that causes allergies. Training the T-Cells to recognize things as benign usually involves modifying the MHC loci and countless other features.

[The Thing]

Okay, sorry for reviving this ancient thread again. I have a new question on the subject.

 

Could we create some kind of...thing (antibody, cell, whatever) that can deliver specific chemicals to a tumor site by targetting the high telomerase activity in the cancer cells? If so, what kind of...thing can do this and how can it target the telomerase?

 

Or is it better just to stick with creating antibodies that could order cytotoxic T cells to attack the telomerase-expressing cells (such as pulsing dendritic cells with telomerase proteins)?

 

EDIT: Also, is it possible , instead of targetting telomerase, to target angiogenin during tumor angiogenesis with the same methods (monoclonal antibodies or creating antibodies that orders cytotoxic T cells to attack cells expressing angiogenin)? However, is angiogenin highly expressed (as much as during tumor angiogenesis) during normal blood vessel growth? If so then I'm sure we don't want to target it.

 

Thanks.

[Kylonicus]

So, are you saying Dak, that essentially, telomerase is prevalent in most cells?

 

If so, if something could penetrate all the cells without damaging them, and eliminate this inhibitor, do you think it could reverse aging?

[ecoli]

So' date=' are you saying Dak, that essentially, telomerase is prevalent in most cells?

 

If so, if something could penetrate all the cells without damaging them, and eliminate this inhibitor, do you think it could reverse aging?[/quote']

 

probably not reverse aging, but maybe slow it down. However, telomerase has the unfortunate side effect of causing cancer in cells it's usually inhibited in.