4 ms·

I don't think it's our model of 'cancer' that is wrong - we can recreate it in lab, we know quite a bit about it, even though it's extraordinarily disingenuous

by toufka 9y ago

I don't think it's our model of 'cancer' that is wrong - we can recreate it in lab, we know quite a bit about it, even though it's extraordinarily disingenuous to call it a single thing. Our model for developing drugs is stuck. Small molecules were unbelievably (literally) useful against invaders of our bodies. They can discriminate and interupt vital processes of one biology without effecting another's biology. This made the development of small molecule drugs in the 20th century against bacteria, fungi, and even some viruses verry effective. Cancer is you. There is no biologically 'other' one can use as a discriminant that doesn't apply equally somewhere else in you. Socially we've built an entire pharmaceutical industry whose talents are focused entirely on a methodology for finding 'interruptors' of foreign disease. And again, that is not cancer. Look the the new CAR-T therapies for cures to cancer. They disrupt the pharmaceutical industry's methodologies in thier development. There can't be a tox test or a primate study. They are fundamentally customizable, cheap, and curative, but they are the injection of genetically modified immune cells containing invented and designed protein tools - not small molecules. There is literally not yet a vocabulary to distinguish these new therapies from the drugs of the 20th century. They are as distinct from drugs as vaccines - but have literally only been tested on a few hundred people, being approved by the FDA only in the past two months.

L_Rahman 9y ago
Hi /u/toufka, do you have any papers or summaries of CAR-T you'd recommend? The first-level Google results are all PR-heavy so I'm hoping you can share something more granular and explanatory.
- pas 9y ago
  https://www.cancer.gov/about-cancer/treatment/research/car-t-cells https://www.cancer.gov/about-cancer/treatment/research/car-t... https://www.reddit.com/r/medicine/comments/6x6q6v/fda_approves_novartis_car_tcell_therapy_for/ https://www.reddit.com/r/medicine/comments/6x6q6v/fda_approv... https://www.reddit.com/r/Futurology/comments/6wqtc8/mass_general_team_reports_first_complete/ https://www.reddit.com/r/Futurology/comments/6wqtc8/mass_gen...
- toufka 9y ago
  /u/pas has some good links below. The primer is that a CAR is an engineered protein that is inserted into your immune cells with a kind of 'cellular surgery'. Here proteins are the actual machines that accomplish life's tasks within a cell - where small molecules are the fuel, building blocks, and modulators of proteins. From inside the linked reddit post, here's a kind of diagram of the designed CAR from a high-level abstraction layer: https://serotiny.bio/notes/proteins/car19/ https://serotiny.bio/notes/proteins/car19/ These proteins can have additive functions in precisely the way small molecules cannot; they can provide new capabilities to cells - whereas small molecule drugs are almost only capable of disrupting an existing capability. The reason these engineered proteins are useful now is that we now have not only have arbitrary read access to genomic information, but with recent advances, we also have arbitrary (and economical) write access to DNA that is long enough to encode an entire protein's blueprint (chemical DNA synthesis). And with those capabilities we've rapidly developed the first novel biological tools to deliver that DNA in a biological way (CRISPR). Until recently we could read an entire blueprint, but we could only make copy/paste changes. We can now design them de novo - and to interesting effect. There is a gene for human hemoglobin out there that is v1.1 - it is actually an intelligent improvement upon our existing human 1.0 version of hemoglobin, in that it can not only not aggregate in a way that causes sickle cell disease, but it can disaggregate mal-formed hemoglobin, inhibiting the disease. We can now start to program those new tools into biology in well-designed ways. Further, with a decade of read-access to life's various genomes, we have started to actually be able to inspect well-written code in other organisms for inspiration. And combining a few of these technologies, we can now start to think about attacking cancer and the like from first principles rather than simply repurposing our small-molecule hammer... And in their preliminary results they have performed remarkably well. Some more discussion: http://www.onclive.com/web-exclusives/expert-discusses-approval-of-first-car-tcell-therapy http://www.onclive.com/web-exclusives/expert-discusses-appro... https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/u...
  - L_Rahman 9y ago
    Thanks for putting the links together. If I understand this correctly (my biomedical engineering undergrad finally coming to use!): 1. Cancer cells present antigens that are specific to cancer cells and do not occur in healthy cells. 2. CRISPR allows us to genetically engineer someone's existing T cells to target those antigens. 3. When re-introduced, these T-cells target the cancer cells and destroy the tumor. 4. Because they are T-cells, they're effectively distributed through blood to the entire body and are able to affect cancerous cells that may be too small to observe or detect. 5. They become inactive and stowaway in the lymphatic system but if the cancer comes out of remission, an "immunity" type response brings them back. This is amazing. This feels like science fiction from my childhood and the life changing possibilities unlocked by CRISPR that I was taught in my undergrad classes.

by toufka 9y ago

L_Rahman 9y ago

Hi /u/toufka, do you have any papers or summaries of CAR-T you'd recommend? The first-level Google results are all PR-heavy so I'm hoping you can share something more granular and explanatory.

pas 9y ago
https://www.cancer.gov/about-cancer/treatment/research/car-t-cells https://www.cancer.gov/about-cancer/treatment/research/car-t... https://www.reddit.com/r/medicine/comments/6x6q6v/fda_approves_novartis_car_tcell_therapy_for/ https://www.reddit.com/r/medicine/comments/6x6q6v/fda_approv... https://www.reddit.com/r/Futurology/comments/6wqtc8/mass_general_team_reports_first_complete/ https://www.reddit.com/r/Futurology/comments/6wqtc8/mass_gen...
toufka 9y ago
/u/pas has some good links below. The primer is that a CAR is an engineered protein that is inserted into your immune cells with a kind of 'cellular surgery'. Here proteins are the actual machines that accomplish life's tasks within a cell - where small molecules are the fuel, building blocks, and modulators of proteins. From inside the linked reddit post, here's a kind of diagram of the designed CAR from a high-level abstraction layer: https://serotiny.bio/notes/proteins/car19/ https://serotiny.bio/notes/proteins/car19/ These proteins can have additive functions in precisely the way small molecules cannot; they can provide new capabilities to cells - whereas small molecule drugs are almost only capable of disrupting an existing capability. The reason these engineered proteins are useful now is that we now have not only have arbitrary read access to genomic information, but with recent advances, we also have arbitrary (and economical) write access to DNA that is long enough to encode an entire protein's blueprint (chemical DNA synthesis). And with those capabilities we've rapidly developed the first novel biological tools to deliver that DNA in a biological way (CRISPR). Until recently we could read an entire blueprint, but we could only make copy/paste changes. We can now design them de novo - and to interesting effect. There is a gene for human hemoglobin out there that is v1.1 - it is actually an intelligent improvement upon our existing human 1.0 version of hemoglobin, in that it can not only not aggregate in a way that causes sickle cell disease, but it can disaggregate mal-formed hemoglobin, inhibiting the disease. We can now start to program those new tools into biology in well-designed ways. Further, with a decade of read-access to life's various genomes, we have started to actually be able to inspect well-written code in other organisms for inspiration. And combining a few of these technologies, we can now start to think about attacking cancer and the like from first principles rather than simply repurposing our small-molecule hammer... And in their preliminary results they have performed remarkably well. Some more discussion: http://www.onclive.com/web-exclusives/expert-discusses-approval-of-first-car-tcell-therapy http://www.onclive.com/web-exclusives/expert-discusses-appro... https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/u...
- L_Rahman 9y ago
  Thanks for putting the links together. If I understand this correctly (my biomedical engineering undergrad finally coming to use!): 1. Cancer cells present antigens that are specific to cancer cells and do not occur in healthy cells. 2. CRISPR allows us to genetically engineer someone's existing T cells to target those antigens. 3. When re-introduced, these T-cells target the cancer cells and destroy the tumor. 4. Because they are T-cells, they're effectively distributed through blood to the entire body and are able to affect cancerous cells that may be too small to observe or detect. 5. They become inactive and stowaway in the lymphatic system but if the cancer comes out of remission, an "immunity" type response brings them back. This is amazing. This feels like science fiction from my childhood and the life changing possibilities unlocked by CRISPR that I was taught in my undergrad classes.