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I question whether it is possible to get the proper
antigen markers in different mutations of the
same cell, even into the same cancer type. |
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I also question whether it is possible to prepare
and store a sufficiently large selection of
mutations. |
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Finally, I question the advantage of doing the first
portion over doing the same thing with
concurrently extracted cells (even most
"inoperable" tumors can be biopsied). |
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I'll admit that that last argument doesn't apply to a
true vaccination approach, but the first two
definitely do, especially the second with regards
to the number of vaccinations required. |
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//extract and grow up some of your immune cells to target cells of that specific cell cancer type in your frozen-line// |
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If this would work then why can't you just do the same thing with cells taken from a biopsy? |
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(Edit: I think [MechE] is saying the same thing too.) |
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Presumably the author is suggesting that cells harvested at
an early age may have attributes not present in the cells
harvested yesterday by your oncologist. |
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This is not such a stupid idea. |
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But, in line with what [MechE] said, I'm not sure it
would work. Cancers are incredibly diverse -
between cancer types, between patients, and
even between subpopulations of cells within a
patient. Those subpopulations are constantly
shifting in response to selective pressure, which
will be different in vivo and ex vivo. So, your in
vitro renal carcinoma might differ substantially
from the cancer you eventually develop. |
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But [+] because it's still not a bad idea. |
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Right, since cancer is ever changing, the idea here is to catch them at the moments of oncogenesis (which who knows how long since the switch from a biopsy, or how many concurrent mutations have occurred) and freeze them with many inititial states of different oncogenic antigen presenting profiles that are mutation-specific. This is so that it is more correlated with the original cell type and provides more targets. It will be easier to culture known cell types then ones that have been cancerous for some time, with an unknown number of mutations. |
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Thus, the training immune reactions are not on a specific antigen state from a biopsy, which likely will have changed, but have many lateral target antigens from an array of possibilities linked to the original cells. |
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Also, it is worth mentioning that de-nucleating these cells -> injecting them may be a good way to raise a safe immune response against these antigens without causing cancer. |
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I say bun if it would work, bone if it wouldn't. |
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// cells harvested at an early age may have attributes not
present in the cells harvested yesterday by your oncologist.
// |
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Or vice-versa. It didn't occur to me until now that cancer is
kind of a backwards disease. From an abstract problem-
solving
point of view, this idea makes perfect sense: go back to
before there was a problem and start building your solution
from there. |
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[leiny], I think you're assuming that some initial
stage of oncogenesis (in the cultured cells) has
unique properties which will be recapitulated in
subsequent cancers. |
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Cells induced into a cancerous state in vitro will
have any of many different possible phenotypes.
Likewise, cancerous cells in the body (even for a
given cell type) will have any of many different
possible phenotypes. |
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Moreover, it's probable that the differing
conditions between tissue culture and in situ
growth will mean that the properties are even less
likely to be similar. |
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If I understand correctly, the aim is to use
transformed cultured cells as a sort of vaccine to
stimulate an immune response against a cancer.
But, if this is the aim, biopsied cells from the
cancer itself will be the likeliest to raise a
relevant immune response and, I believe, this
approach has been tried already. |
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[MB] So you're saying that would be no correlation in antigen profile after specific induction of frameshift mutation in a tumor suppressor although 1) same gene, with the 2) same cell types, in the 3) same culture environment 4) same person 5) same time frozen after mutation (just after oncogenesis)? |
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Not sure if this experiment has been done and I think your assumption of variability is a little hand-wavy. Its a reasonable hypothesis to expect some correlations and s.s. differences, between cell types and/or mutations-induced. |
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In a nutshell the problem with cancers is that the immune system does not detect or respond to them (enough) whereas for many disease conditions the immune system actually over reacts allowing us to use vaccines. On an essential level, no matter how high the exposure to the cancer becomes the immune system will never arrive at a healthy "kill those cells, but not the others" type of response. Since you seem to be proposing that somehow we can create a more powerful immune trigger than the actual full blown metastasizing cancer can, I would love to understand better what mechanism you think will be operating. In cases where viral infections are a co-factor in cancer then our best response is to prevent the virus from taking hold because in these cases we have diseased cells we can muster an immune response to. |
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[WcW] That is not entirely true. It is theoretically
possible to induce an immune response to a
cancer. This has been achieved in vitro and in lab
animals. There are several companies that are
trying to make the transition to humans. |
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You are absolutely right that the trick is to induce
a sufficiently strong immune response, and
several different methods are being used for this.
Those that I'm aware of are training immune cells
to attack cells with specific over expressed
proteins, or extracting and and purifying the cells,
and then exposing them to the cancer during the
stage where they would normally become
sensitive to a particular target. (ImmunoCellular,
Celldex, and Northwest Biotherapuetics that I am
aware of, full disclosure, I have a bit of money
invested in that last.) |
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//So you're saying that would be no correlation in
antigen profile after specific induction of
frameshift mutation in a tumor suppressor
although 1) same gene, with the 2) same cell
types, in the 3) same culture environment 4) same
person 5) same time frozen after mutation (just
after oncogenesis)?// |
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Yes, pretty much. Actually, the point I'm making
is a bit more complex than that. For a cell to
become cancerous, it has to acquire a whole host
of mutations. |
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For any given cell type in any given tissue, there
are many possible combinations genes that can be
mutated to throw the switch. |
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And for each of those genes, there are usually a
number of specific mutations that can happen. |
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Thus, a priori, two cancers (of a given cell type)
are likely to differ very significantly in their
molecular phenotypes. |
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But then you have to add in another factor. The
environment of cells in the body is radically
different from their environment in tissue
culture. Therefore, the set of mutations they
need in order to survive and proliferate is also
very different. |
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On balance, therefore, cells immortalized in vitro
will be very different from the cells in a cancer. |
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As I mentioned earlier, the best chance for this
type of therapy is to take a biopsy of the actual
cancer, and manipulate in such a way as to make
it antigenic, and use it as a sort of vaccine. |
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Fascinating. What do you think about inducing a tumor to 'think' it is in skeletal muscle tissue so that the uncontrolled cell division heals damage and then becomes benign? |
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Since watching Eva Vertes TED talk on the subject, I've been waiting for some follow-up research.
Any chance you've heard something I haven't been able to find? |
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//. What do you think about inducing a tumor to
'think' it is in skeletal muscle tissue so that the
uncontrolled cell division heals damage and then
becomes benign?// |
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I don't know - has someone been trying that? It's
likely to be difficult, because a cancerous cell is
already screwed up, and probably exhibiting a
bunch of incomplete patterns of differentiation
(ie, it may have weird features normally
associated with several other cell types). |
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You might be able to get a cancer cell to behave
like a pluripotent stem cell, and then use it for
interesting things. But a priori (and reticulo
equator) it seems a less promising approach than
using stem cells from the start. |
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// I don't know - has someone been trying that? // |
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Yes. Well this girl Eva,(only nineteen at the time), wondered why skeletal muscle tissue doesn't get cancer. She discovered that every cut or torn muscle does indeed get cancerous cell division which heals the wound and then turns off. She figures that, as a species, we have not needed a way to tell cancer to turn off within our organs or other parts because it is not necessary in order to make it to the age of grandparents.
Evolutionarily speaking we don't need to live any longer than it takes to ensure the next generations' survival.
[link]
But if we could trick cancer into thinking it was in skeletal muscle tissue then cancer may be made to be a cure. |
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How's that for out-of-the-box thinking eh? |
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My understanding is that skeletal muscle does not
heal in the way skin or bone heals. It just scars.
The muscle cells do not divide and multiply. Bigger
biceps means bigger cells, not more of them. Not
ever dividing is a great way to keep from becoming
cancer. |
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Little kids who are growing new skeletal muscle
cells can get tumors of muscle -
rhabdomyosarcoma. These are rare in adults. |
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Other tumors, of course, have no trouble at all with
skeletal muscle as a home to live and grow in. |
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Re the idea - I heard that if you are in a lab in the
business of transforming cells to make them
immortal in petri dishes, you should not use your
own cells as starting material - although they are
very handy and come cheap, there could be a risk of
getting the immortalized cells back into your body
as a sort of zombie homecoming. |
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And to speculate at a 45 degree angle to this idea, I
think something of this sort might be responsible
for the Caulerpa strain of seaweed which is taking
over the mediterranean. One would think a
hothouse flower would have trouble in the real
jungle but maybe not - maybe life in vitro allowed
this plant (and so maybe the cells in a dish) to
jettison useless old baggage and rulebooks on
playing nice. |
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In this scenario, it is our bodies that are the
Mediterranean. And it is not the cancer cells that
we want forgetting the rules and turning strong and
strange - it is our immune cells. This premise
underlies some of the new successful antimelanoma
theories - that we will have a more interesting and
action packed homecoming dance if we send all the
chaperones home. |
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The tissues that arise might be deranged and detectable in numerous ways, but the metastasized stem cells from the line simply have a very bad idea, which is impossible to determine from the outside of the cell. Your immune system is pretty good at picking out tissues that show signs of being in the wrong place which is why immune suppressed individuals suffer more and novel types of cancers. So it's a yes/no type of situation. If the immune system is excessively sensitive to native cells you have auto-immunity issues, and if it isn't sufficiently sensitive to native cell aberrations more cancerous tissues will totally escape it. I would question if the immune system can ever pick out the stem cell line though, since these cells are essentially indistinguishable from their healthy counterparts. Also, not all cancers have apoptosis dysfunctions, they are not all "immortal" cells. |
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