Possible cure for Leukemia

[destrekor]

Well the plot for I Am Legend was that they made a vaccine for cancer (which people are currently making)... this one they just mutated the person's cells to target Leukemia.

In I Am Legend, they altered a virus to target cancer, actually. Specifically, the measles virus.

 

[destrekor]

So they really are trading cancer for aids. Since it self replicates, it can be spread to other people just like traditional hiv can.

You have as much chance of spreading a dead shell of HIV as you do a dead shell of an influenza virus - which is to say, no, it's not happening.

They aren't using live HIV, they are using a more or less inert and modified HIV to inject specific code into T cells.
After that process, the whole HIV thing is also completely out of the picture. It's the modified T cells (modified with certain genetic code, they don't contain anything HIV) that are then returned into the body, and those T cells replicate.

Which is what T cells do once they are activated in the body... that is, they replicate. Unless I am mistaken?

They'll eventually be "used up", leaving fewer of them remaining. Eventually, without successive treatments, "natural" T cells will make up the entirety of the "T cell population."


I guess one question: in time, as the B-cell-killing T cells drop in number and get replaced with regular T cells, do B cells make their comeback? I figure after this kind of treatment, the body still continues to produce B cells, but they are killed by the modified T cells. Eventually, as I understand it, the modified T cells drop in number, which allow the B cells to gain in number as less and less of them are killed off. Eventually, that destruction simply stops happening.

At that rate, is the immune system essentially returned to a blank baseline?

They say natural immunity is shot when the B cells are gone. But what about when they return? Are the new ones produced by the body helping by providing remembered immunity?
Is it B cells that hold onto specific proteins that act as the true mark of immunity? So, are new ones "blank" - not providing immunity against anything until specific B cells capture onto something with which to identify baddies for activation of immune response upon next encounter?



In short, does the ability to even have the typical immune system, at the minimum, return in time as the modified T cells disappear? And as the basic immune system returns, is it in that initial "infantile" state, awaiting encounters with baddies from which it can "learn immunity", but having no learned immunity at that point in time?

 

[Gibsons]

So they really are trading cancer for aids. Since it self replicates, it can be spread to other people just like traditional hiv can.

No, this wouldn't be infectious.

 

[Gibsons]

A distinction isn't useful since prognosis and therapy doesn't change. It's more useful to group them by histology and immunologic markers than site of occurrence.

Prognosis and therapy doesn't change according to what? The prognosis and therapy varies tremendously between CLL, ALL, CML, TAL etc.

People have been trying to use viral vectors to target cancer (among other things) for decades. It never seems to pan out in the end. I'd be skeptical.

The virus in this case is just a vector to get a gene into T cells. The T cells do the killing after that.

 

[destrekor]

Prognosis and therapy doesn't change according to what? The prognosis and therapy varies tremendously between CLL, ALL, CML, TAL etc.



The virus in this case is just a vector to get a gene into T cells. The T cells do the killing after that.

And honestly, it's a damn good idea to use viruses as a vector for this kind of stuff. Why? As long as you aren't directly introducing any modified viruses into the host, i.e. you use them to simply do one job and throw them out, then you're basically taking one of the best genetic hacking tools nature has ever created.

Viruses are basically the genetic hacking/splicing tool of nature. If we can make them do our bidding, we gain a huge advantage in the medical world: we can thus indirectly hack into cells and into genomes.
The trick is finding the best hacking tool for specific jobs.


They're already looking at doing a similar thing, iirc, with rods and cones in the eye. Though I might have dreamed that, which is very much possible.
I await the day we can cure color deficiency. It's a fairly low priority in the medical world, but it's a great first step for genetic hacking. And I would love it personally, seeing as I could personally use such a hack.

 

[Gibsons]

Which is what T cells do once they are activated in the body... that is, they replicate. Unless I am mistaken?

Yes, they'll replicate to some degree.

They'll eventually be "used up", leaving fewer of them remaining. Eventually, without successive treatments, "natural" T cells will make up the entirety of the "T cell population."

I don't think it's known how long the new population of T cells will persist.

I guess one question: in time, as the B-cell-killing T cells drop in number and get replaced with regular T cells, do B cells make their comeback? I figure after this kind of treatment, the body still continues to produce B cells, but they are killed by the modified T cells. Eventually, as I understand it, the modified T cells drop in number, which allow the B cells to gain in number as less and less of them are killed off. Eventually, that destruction simply stops happening.

Right, just depends on how long the altered T cells persist and remain effective.

At that rate, is the immune system essentially returned to a blank baseline?

Not quite, the T cell compartment will still have its memory cells, but all memory B cells are probably gone.

They say natural immunity is shot when the B cells are gone. But what about when they return? Are the new ones produced by the body helping by providing remembered immunity?

Assuming they do come back, all the new B cells should be naive.

Is it B cells that hold onto specific proteins that act as the true mark of immunity?

I wouldn't say there's one single 'true mark' of immunity like that. There are T cells and lots of other cells. Specific antibody has been and is used frequently simply because it's easy to measure.

So, are new ones "blank" - not providing immunity against anything until specific B cells capture onto something with which to identify baddies for activation of immune response upon next encounter?

That's probably correct but there are lots of subtleties beyond that as well. For instance, a lot of children are highly susceptible to ear infections, but grow out of it. This might have something to do with a refinement of the B cell response and antibody repertoire - so do these patients have to go through that phase again? Could be.

In short, does the ability to even have the typical immune system, at the minimum, return in time as the modified T cells disappear? And as the basic immune system returns, is it in that initial "infantile" state, awaiting encounters with baddies from which it can "learn immunity", but having no learned immunity at that point in time?

They'll have learned immunity in the form of T cells, but not B cells. So not a completely naive immune system. How much this matters will likely depend on the disease.

 

[destrekor]

Yes, they'll replicate to some degree.



I don't think it's known how long the new population of T cells will persist.



Right, just depends on how long the altered T cells persist and remain effective.


Not quite, the T cell compartment will still have its memory cells, but all memory B cells are probably gone.



Assuming they do come back, all the new B cells should be naive.


I wouldn't say there's one single 'true mark' of immunity like that. There are T cells and lots of other cells. Specific antibody has been and is used frequently simply because it's easy to measure.


That's probably correct but there are lots of subtleties beyond that as well. For instance, a lot of children are highly susceptible to ear infections, but grow out of it. This might have something to do with a refinement of the B cell response and antibody repertoire - so do these patients have to go through that phase again? Could be.


They'll have learned immunity in the form of T cells, but not B cells. So not a completely naive immune system. How much this matters will likely depend on the disease.

Got it.

Yeah they discussed a vague concept of depletion of modified T cells over time, so I was using that as a basis. But it's a new approach with some different results and number of applications for each individual, so there is a lot of ambiguity in the knowledge they even have. It's definitely case by case with a fair bit of guesswork it seems (not downplaying the situation or accomplishments by any means!).

I will completely admit to an ignorance of specific immune system cells, functions of each cell, how each group of cells breaks down into specific types, how they behave upon activation, how they activate, etc etc etc etc.
I have a general knowledge, most specifics long since forgotten (and never even knew the larger majority of specifics - I had maybe a few courses of this in schooling, and some self-education/reading of research/general interest). So yeah, I figured I was on the right track but would be completely way off base once it was attacked with specifics. Which is why I approached it the way I did.

And I appreciate the clarifications. This stuff is just too damn cool to say "welp, this is confusing. I'm outtie!" though eventually I'll reach that point in any discussion or research sidetrack.

 

[Pens1566]

A distinction isn't useful since prognosis and therapy doesn't change. It's more useful to group them by histology and immunologic markers than site of occurrence.

People have been trying to use viral vectors to target cancer (among other things) for decades. It never seems to pan out in the end. I'd be skeptical.

Prognosis and therapy are vastly different between different leukemias (and even age of patient), let alone adding in hodgkins' and non-hodgkins' lymphoma.

 

[CottonRabbit]

Prognosis and therapy doesn't change according to what? The prognosis and therapy varies tremendously between CLL, ALL, CML, TAL etc.

Doesn't change depending on whether it's leukemia or lymphoma, which is why the WHO changed the classification. Of course they vary depending on what leukemia, but I was responding to the original post about the WHO's merging of leukemias and lymphomas. For example in this case, B-cell acute lymphoblastic leukemia has been re-categorized to B-ALL/LBL, reflecting the fact that both the leukemia and lymphoblastic lymphoma (LBL) have the same markers and look the same under a microscope. Another example would be the merging of CLL (a leukemia) with SLL (a lymphoma) to CLL/SLL.

Prognosis and therapy are vastly different between different leukemias (and even age of patient), let alone adding in hodgkins' and non-hodgkins' lymphoma.

Never said they didn't. See above.

 

[Gibsons]

Doesn't change depending on whether it's leukemia or lymphoma, which is why the WHO changed the classification. Of course they vary depending on what leukemia, but I was responding to the original post about the WHO's merging of leukemias and lymphomas. For example in this case, B-cell acute lymphoblastic leukemia has been re-categorized to B-ALL/LBL, reflecting the fact that both the leukemia and lymphoblastic lymphoma (LBL) have the same markers and look the same under a microscope. Another example would be the merging of CLL (a leukemia) with SLL (a lymphoma) to CLL/SLL.



Never said they didn't. See above.

okay, now I understand what you're saying. The first post implied that all the hematologic malignancies were the same.... or something. Made no sense to me. Note that Pens apparently got the same impression.

 

[SaDiZTiKStyLeZ]

Kill off everyone who has cancer. And everyone who has aids/hiv. Problem solved.

 

[DCal430]

Should work for any B cell cancer.

The general method is adaptable for most kinds of cancer, you just change the targeting molecule. But as I mentioned above, you probably have to deal with targeting normal cells as well. Not an option for say, liver cancer.



They've tested it on B CLL and B ALL, seems to work for both. Should work equally well (with the same side effects) on HCL, DLCBCL, etc.



wat. Has WHO lost its collective mind or is something getting lost in translation?

One issue you have is the distinction between Leukemia and Lymphoma can be very arbitrary.

You can have a patient and some doctors will say they have Chronic Lymphocytic Leukemia, while other doctors will say they have Small Lymphocytic Lymphoma. Which is why these are now viewed as essentially the same cancer.

Same with B-Cell ALL and B-Cell LL you can have a patient that some doctors will say has B-Cell Acute Lymphoblastic Leukemia, while other doctors will say has B-Cell Lymphoblastic Lymphoma. Because the distinction is arbitrary. WHO know says these are essentially the same cancer.

 

[Gibsons]

One issue you have is the distinction between Leukemia and Lymphoma can be very arbitrary.

You can have a patient and some doctors will say they have Chronic Lymphocytic Leukemia, while other doctors will say they have Small Lymphocytic Lymphoma. Which is why these are now viewed as essentially the same cancer.

Same with B-Cell ALL and B-Cell LL you can have a patient that some doctors will say has B-Cell Acute Lymphoblastic Leukemia, while other doctors will say has B-Cell Lymphoblastic Lymphoma. Because the distinction is arbitrary. WHO know says these are essentially the same cancer.

Already covered a few posts up.

 

[Sonikku]

Using the one to destroy the other! Of course! It's so simple!

 

[sao123]

Yes, they'll replicate to some degree.



I don't think it's known how long the new population of T cells will persist.



Right, just depends on how long the altered T cells persist and remain effective.


Not quite, the T cell compartment will still have its memory cells, but all memory B cells are probably gone.



Assuming they do come back, all the new B cells should be naive.


I wouldn't say there's one single 'true mark' of immunity like that. There are T cells and lots of other cells. Specific antibody has been and is used frequently simply because it's easy to measure.


That's probably correct but there are lots of subtleties beyond that as well. For instance, a lot of children are highly susceptible to ear infections, but grow out of it. This might have something to do with a refinement of the B cell response and antibody repertoire - so do these patients have to go through that phase again? Could be.


They'll have learned immunity in the form of T cells, but not B cells. So not a completely naive immune system. How much this matters will likely depend on the disease.

sounds like such a treated person will need to be revaccinated as a child, but then will that even be safe with a weakened immune system?

 

[Gibsons]

sounds like such a treated person will need to be revaccinated as a child, but then will that even be safe with a weakened immune system?

Vaccines would either be pointless (they can't make antibodies to the vaccine) or maybe dangerous.

You could give them serum from someone who's recently been vaccinated (or recovered from the infection), but the protection would only last a week or two, if that.

 

[DCal430]

okay, now I understand what you're saying. The first post implied that all the hematologic malignancies were the same.... or something. Made no sense to me. Note that Pens apparently got the same impression.

Oh noo, didn't mean that all hematologic malignancies were the same, because they aren't. I meant the distinction between Leukemia and Lymphoma in the broader sense isn't meaningful, but within the hematologic malignancies there are meaningful difference.

Lymphoplasmacytic Lymphoma for example is very different than Lymphoblastic Lymphoma. Whose treatment and prognosis is vastly different.

 

[sao123]

Vaccines would either be pointless (they can't make antibodies to the vaccine) or maybe dangerous.

You could give them serum from someone who's recently been vaccinated (or recovered from the infection), but the protection would only last a week or two, if that.

wait... wouldnt the naive new B cells be able to discover and remember the reintroduced vaccine?

I was understanding your post to mean current B cell memories would be gone, not the ability for future B cells to continue to create memories.

 

[Sho'Nuff]

That's encouraging news indeed and I hope they do find a cure for Cancer too.

There are thousands of types of cancer with millions of different variations. There will never be a "single" cure for "all" cancer. At least not in our lifetime.

On another note, I do hope that this development in Leukemia research produces good results. In the last 10 years, I've known 10 people who have died from it.

 

[Gibsons]

wait... wouldnt the naive new B cells be able to discover and remember the reintroduced vaccine?

I was understanding your post to mean current B cell memories would be gone, not the ability for future B cells to continue to create memories.

Naive new B cells will be killed before they can see the reintroduced vaccine as long as these altered T cells are around. The bone marrow will produce these new cells constantly and they'll be killed constantly. The future B cells will only be able to create new memory if they're allowed to live.

Some vaccines however (measles, some others) create T cell memory (along with B cell). That T cell memory is probably still there, and might be enough for protection.

On the bright side, they shouldn't have any allergies. Except to poison ivy and things like that.

edit - oh yeah, for blood transfusions, they should all be universal acceptors now, even if they're O+.

 

[destrekor]

Naive new B cells will be killed before they can see the reintroduced vaccine as long as these altered T cells are around. The bone marrow will produce these new cells constantly and they'll be killed constantly. The future B cells will only be able to create new memory if they're allowed to live.

Some vaccines however (measles, some others) create T cell memory (along with B cell). That T cell memory is probably still there, and might be enough for protection.

On the bright side, they shouldn't have any allergies. Except to poison ivy and things like that.

edit - oh yeah, for blood transfusions, they should all be universal acceptors now, even if they're O+.

Is that how allergies are determined? By B cell's interacting with the newly-introduced proteins?

I know most allergies are based around proteins and how some part of the body responds to said protein, but never understood where the memory/"I hate that protein!" part comes from.

What about medication allergies? I'm fairly certain I had a dermatological response to Zithromax (as in, pretty sure I had mild hives, so I've always said I'm allergic to it now, just in case I am, and for fear a second reaction would be worse)

And is poison ivy, as an allergy, determined by means not like other allergies?
Not all humans are allergic to poison ivy, which is why I ask.
I still don't know if I am. I'm terrible at plant identification, so no idea if I've actually brushed up against it or not - I've been near it, that's for sure.

 

[Gibsons]

Is that how allergies are determined? By B cell's interacting with the newly-introduced proteins?

For most allergies, (hay fever, food allergies, etc) what's going on is that B cells are producing IgE antibodies specific for that antigen rather than some or any other type of antibody (IgM, IgG, IgA or even IgD). IgE binding to that foreign thing is what causes histamine (and other things) to be released, leading to sneezing, wheezing, runny nose, hives, whatever.

IgE is considered to be an antibody specialized for parasites. The production of IgE against food or pollen or whatever seems to be the result of a mistake somewhere along the line. What causes this mistake is still not fully understood, there are some genetic predispositions, then there are some that seem to just happen.

What about medication allergies? I'm fairly certain I had a dermatological response to Zithromax (as in, pretty sure I had mild hives, so I've always said I'm allergic to it now, just in case I am, and for fear a second reaction would be worse)

In most cases, there's an odd off-reaction or something of the drug with some normal self protein. The protein is then recognized as non-self, and there's an immune response.

I haven't read up on this stuff in a long time, so my info here might be a bit shaky or out of date.

And is poison ivy, as an allergy, determined by means not like other allergies?

It's very different in that it's antibody independent. It seems to happen due to macrophages and some specialized T cells. No B cell or antibody required. This is the main reason the reaction takes longer (about 24 hours) to develop.

I wish we could use a different word for the reaction than 'allergy.' In immunology terms, hay fever is a "Type I hypersensitivity" and poison ivy is a "Type IV." Also, it bugs me when people talk about an "immunity" to poison ivy. You can argue that the people who develop a rash are immune, because they mount an immune response! Reactive and non-reactive would be better terms. /nod

Not all humans are allergic to poison ivy, which is why I ask.
I still don't know if I am. I'm terrible at plant identification, so no idea if I've actually brushed up against it or not - I've been near it, that's for sure.

I recommend you don't try to find out. I suspect no one is reactive on their first exposure, but most are on the second. Maybe some people are never reactive, but I haven't seen anything to really answer that question.