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It has been proposed to use antibodies to direct chemotherapy drugs only to cancerous cells, leaving healthy cells alone. The problem with this is that cancer cells are very diverse, so it's very difficult to find a cancer-specific antigen that's found in all cancer cells. If I've understood correctly...
However,
cancer cells are derived from non-cancer cells, which *do* have specific antigens that can be used. By using antibodies, it should be possible to localise the drugs to cells of a particular tissue type, including any cancer cells derived from them - so chemotherapy for bowel cancer would target all cells derived from, say, the epithelial lining, rather than all rapidly dividing cells in the body. Whilst this would still have severe side effects, my hope is that by using immunolabeling they would be limited only to that tissue, rather than affecting other tissues. So not perfect, but better than current treatment.
This is contingent upon two things - (1) that specific tissues can be targeted, and (2) that cancer cells retain tissue specific antigens.
Antibody cancer therapeutics
http://www.mayoclin...tibody/art-20047808
It is a good idea. It has been around for a while. [bungston, Feb 24 2017]
[link]
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They've also thought of the opposite approach, where you conjugate an activating enzyme (e.g., glucuronidase) to a tumour-specific antibody and then you administer the pro-drug (e.g., the glucuronide) to the patient. The idea is to reduce the side-effects of the drug by only activating it in the presence of the cancerous tissue. |
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My understanding of current monoclonal antibody treatments is that they're dependent on having a tumour-specific antibody, which isn't a given. I'm suggesting that it would be easier to target the cell type that the cancer is derived from - not as good as targeting the cancer cells directly, but much better than targeting every cell in the body, and perhaps opening up possibilities for treating metastasised cancers where ordinary treatment would kill the patient. |
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Antibody treatments work as you propose here. None rely on a tumor specific antibody. All of them hit normal tissue antigens that are either overexpressed on cancer or more important to cancer. Examples are lymphoma antibodies hitting CD20, CD30, CD52. Those antibodies also kill the normal lymphocytes with those antigens, with the ill effects dependent on how important those normal ones are. |
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Solid tumor treating antiboides include those hitting EGFR and HER2, both also normally expressed on various epithelial tissues. |
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It doesn't always work. One would think PSA would be a fine target since the prostate is dispensable and many prostate cancers have lots of PSA. No dice. |
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Real mutated cancer antigens exist. The ones that come up over and over again are probably those that are the reason for that particular cancer - the sine qua non if I may bust out some latin. They are drivers of some sort. Some have been successfully targeted but by small molecules, not antibodies. The BCR ABL fusion protein driving chronic myelogenous leukemia is the poster child for this approach. |
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True weird freaky cancer antigens certainly exist in great variety. Then why does the immune system not recognize them and kill the freak cell? Because the cancer cell has some fake diplomatic immunity credentials it has forged. This is the target for the new PD1-based immunotherapeutics which are currently being heavily advertised - do away with all diplomatic immunity and see what the cops do then. |
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Woah, [bungston] - kudos for a cogent annotation! |
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The main problem with cancer is that there's way too much biology involved. Cancer cells are usually shades of grey compared to normal cells, not black and white, so hitting their biology selectively is very, very difficult. |
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The simpler (though not necessarily easier) approach is to selectively kill cells based on their genomic sequence. By definition, cancer cells have sequences that normal cells lack, and that _is_ a black and white distinction. The problem then becomes (a) how to kill cells based on their genomic sequence alone and (b) how to tailor such therapeutics to each individual cancer (since every cancer - in every patient - is different). |
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[MB] Would having a very cheap way to synthesise custom RNA strands help there? |
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Plus, of course, a delivery method - viral capsids minus the viral DNA, manufactured by genetically engineered E. coli. Splice in the DNA or RNA you want, and they'll put out capsids containing them. Perhaps it should be another post. |
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//Would having a very cheap way to synthesise custom RNA strands help there? // |
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Not really - RNA and DNA syntheses are already trivially cheap; and RNA isn't a good starting point unless there's no alternative, because the damned stuff falls apart if you look at it funny. |
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But yes, delivery of any therapeutic - especially non-small-molecules - is a major hurdle. |
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Sometimes I've wondered what would happen if we just cultivated someone's cancerous and healthy cells and chucked various viruses at it, trying to evolve one that would wipe out the cancer but not the patient. |
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Other times I've thought we should just inject the cells into animals and try and use their antibodies. |
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I just can't shake the feeling that the Nobel prize for developing a new line of treatments will go to someone who comes up with something that's incredibly obvious in hindsight... |
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//cultivated someone's cancerous and healthy cells and chucked various viruses at it// |
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Possible. But you'd need to do it for each person. |
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//just inject the cells into animals and try and use their antibodies// |
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No, because (a) most of their immune response will be against normal (but non-animal) things, not cancer things and (b) non-human antibodies are terrible therapeutics, because the human immune system sees them as foreign proteins. Hence the development of humanized antibody technology. |
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[MB], doing it for each person shouldn't be a problem nowadays. I imagine you could automate it? Even if you needed to have someone monitoring each single evolver, it would still be cheap compared to current treatments. |
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My comment about RNA was about RNA interference. I was thinking that, if you could get a suitable RNA strand into a cell, it would jam up cell replication if the DNA was complementary, whilst not affecting it otherwise. |
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These ideas should probably go in separate posts... |
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EDIT: okay, RNA interference doesn't work that way. I did know this (undergraduate cell biology), I just forgot. Point is, RNA should be able to interfere with cell replication... |
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<placeholder for smug, derivative annotation plagiarised from other posts after a few more knowledgeable HB'ers have had their say> |
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Naturally, someone's already thought of that. Is there a list anywhere of unsolved issues and proposed solutions? |
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Yes, RNAi-style approaches aren't a dumb idea. Personally, I'm favouring a slightly different approach, and one that doesn't depend on expression of "cancer" sequences. |
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Not all cancers produce novel, cancer-specific transcripts - the key mutations can be in regulatory components (eg,enhancers) for otherwise "normal" genes. So you still don't necessarily get perfect cancer specificity. But all cancers, somewhere, contain a genomic sequence which is not present in normal cells of the same individual. |
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