4 ms·

A primer on the next generation of antibodies

53 points by abhishaike 2y ago

Talkative32 2y ago
[flagged]
frankus 2y ago
I'm curious what the challenges are around using mRNA to synthesize antibodies in a person's own cells. A little googling turned up this company: https://acuitastx.com/technology/mrna-therapeutics/ https://acuitastx.com/technology/mrna-therapeutics/ but I'm curious if there are any obvious showstoppers for that kind of thing.
- typingonmyphone 2y ago
  I assume the main issue is that antibodies are produced by B cells and probably wouldn’t be functional if produced by the muscle cells that are the traditional mRNA target. And it would be transient, your immune system wouldn’t learn to make that antibody (maybe a feature for a drug).
thenerdhead 2y ago
> Potentially, antibodies, as a functional category of therapeutic, may very well be on their way out. I’m a bit confused as to what you reference here but I’m assuming monoclonal (mAbs). I apologize I did not read your prior post. The market estimates are quite optimistic in this category such as: > Antibodies are the dominant class of protein therapeutics with over 160 antibody therapeutics currently licensed globally and a market value expected to reach $445 billion in the next five years https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983868/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983868/ Are you aware that BARDA is investing $5 billion into therapeutics like monoclonals/polyclonal for COVID-19 countermeasures? Their major focus is on many of the problems you stated and they want to drive costs down: https://youtu.be/t9lrPDxLsfw?si=T87jPBinbuTtDad_ https://youtu.be/t9lrPDxLsfw?si=T87jPBinbuTtDad_ Monoclonal antibodies seem like they finally are reaching the golden age based on their use earlier this pandemic, novel findings for rejuvenating our immune system, and even targeting other notable chronic diseases. https://medicalcountermeasures.gov/nextgen/ https://medicalcountermeasures.gov/nextgen/ https://www.nih.gov/news-events/nih-research-matters/rejuvenating-immune-system-depleting-certain-stem-cells https://www.nih.gov/news-events/nih-research-matters/rejuven... https://www.nih.gov/news-events/news-releases/nih-scientists-find-weak-points-epstein-barr-virus https://www.nih.gov/news-events/news-releases/nih-scientists... The primer in the next generation is wonderful. I’d love to see nanobodies created for SCV2 as soon as possible. The interesting part is that these platforms that BARDA are helping get online will help us pivot to any threats and use these next generation vehicles to respond. Keep an eye on vaccines too as they are going through a moment of next generation vehicles as well. I.e. multiple antigens, mucosal deliver, etc.
spondylosaurus 2y ago
Super interesting writeup, thank you! So I know there's a difference between humanized and fully human mAbs, but is the manufacturing process identical between them? Do even human antibodies grow in CHO tanks?
tomohelix 2y ago
A good introduction but it is too narrow on the "science" side and not enough on the regulatory side. I can say this with pretty strong confidence: had the FDA not being so strict about its trials, lots of these experimental type of antibodies would have already received massived research and commercialization. But it is simply so much harder and so much more expensive to push something so different through the pipeline. A million things can go wrong, and even the biggest biopharmas can't handle that level of risk. Drug development, especially biologics, is so expensive it becomes incredibly conservative and resistant to changes. Five guys in a garage can make a tech company that shakes the world. But 10 guys in a lab worth one million dollars trying to make a biologic drug will likely declare bankruptcy by the end of the year, at best. I would say by the end of the month is more likely.
- mjewkes 2y ago
  >I can say this with pretty strong confidence: had the FDA not being so strict about its trials, lots of these experimental type of antibodies would have already received massived research and commercialization If the FDA was not so strict in requiring evidence, medicine would look like the supplement aisle, and the incentive to actually do the stupidly hard work of developing effective drugs & proving their efficacy would disappear. Why even bother investing in developing a complex new antibody if you can sell some mushroom powder from a beach and claim whatever you want about it, ala Tim Ferris & "BrainQUICKEN". There are plently of valid "incremental" critiques about the FDA. IMO, their devices and diagnostics divisions are weaker than CDER and CBER. Even those two (drug focused) divisions can be too slow moving and occasionally capricious about when they want more evidence. But their final decisions are generally pretty good, with a few exceptions. And most of those exceptions are drugs that they approved that they shouldn't have (e.g. Aduhelm) - not vice versa. Can you point at a promising drug candidate with statistically solid efficacy data that CDER or CBER has rejected? Also - note that there are approved scFVs and VHHs and mimetics - as stated in the article. Each is useful in particular situations, but none is some sort of wild medical breakthrough. There is just no evidence that any of these modalities would be attracting extraordinary investment "if only it weren't for the FDA".
  - 2y ago

53 points by abhishaike 2y ago

[flagged]

I'm curious what the challenges are around using mRNA to synthesize antibodies in a person's own cells. A little googling turned up this company: https://acuitastx.com/technology/mrna-therapeutics/ https://acuitastx.com/technology/mrna-therapeutics/ but I'm curious if there are any obvious showstoppers for that kind of thing.

typingonmyphone 2y ago
I assume the main issue is that antibodies are produced by B cells and probably wouldn’t be functional if produced by the muscle cells that are the traditional mRNA target. And it would be transient, your immune system wouldn’t learn to make that antibody (maybe a feature for a drug).

thenerdhead 2y ago

> Potentially, antibodies, as a functional category of therapeutic, may very well be on their way out. I’m a bit confused as to what you reference here but I’m assuming monoclonal (mAbs). I apologize I did not read your prior post. The market estimates are quite optimistic in this category such as: > Antibodies are the dominant class of protein therapeutics with over 160 antibody therapeutics currently licensed globally and a market value expected to reach $445 billion in the next five years https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983868/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983868/ Are you aware that BARDA is investing $5 billion into therapeutics like monoclonals/polyclonal for COVID-19 countermeasures? Their major focus is on many of the problems you stated and they want to drive costs down: https://youtu.be/t9lrPDxLsfw?si=T87jPBinbuTtDad_ https://youtu.be/t9lrPDxLsfw?si=T87jPBinbuTtDad_ Monoclonal antibodies seem like they finally are reaching the golden age based on their use earlier this pandemic, novel findings for rejuvenating our immune system, and even targeting other notable chronic diseases. https://medicalcountermeasures.gov/nextgen/ https://medicalcountermeasures.gov/nextgen/ https://www.nih.gov/news-events/nih-research-matters/rejuvenating-immune-system-depleting-certain-stem-cells https://www.nih.gov/news-events/nih-research-matters/rejuven... https://www.nih.gov/news-events/news-releases/nih-scientists-find-weak-points-epstein-barr-virus https://www.nih.gov/news-events/news-releases/nih-scientists... The primer in the next generation is wonderful. I’d love to see nanobodies created for SCV2 as soon as possible. The interesting part is that these platforms that BARDA are helping get online will help us pivot to any threats and use these next generation vehicles to respond. Keep an eye on vaccines too as they are going through a moment of next generation vehicles as well. I.e. multiple antigens, mucosal deliver, etc.

spondylosaurus 2y ago

Super interesting writeup, thank you! So I know there's a difference between humanized and fully human mAbs, but is the manufacturing process identical between them? Do even human antibodies grow in CHO tanks?

tomohelix 2y ago

A good introduction but it is too narrow on the "science" side and not enough on the regulatory side. I can say this with pretty strong confidence: had the FDA not being so strict about its trials, lots of these experimental type of antibodies would have already received massived research and commercialization. But it is simply so much harder and so much more expensive to push something so different through the pipeline. A million things can go wrong, and even the biggest biopharmas can't handle that level of risk. Drug development, especially biologics, is so expensive it becomes incredibly conservative and resistant to changes. Five guys in a garage can make a tech company that shakes the world. But 10 guys in a lab worth one million dollars trying to make a biologic drug will likely declare bankruptcy by the end of the year, at best. I would say by the end of the month is more likely.

mjewkes 2y ago
>I can say this with pretty strong confidence: had the FDA not being so strict about its trials, lots of these experimental type of antibodies would have already received massived research and commercialization If the FDA was not so strict in requiring evidence, medicine would look like the supplement aisle, and the incentive to actually do the stupidly hard work of developing effective drugs & proving their efficacy would disappear. Why even bother investing in developing a complex new antibody if you can sell some mushroom powder from a beach and claim whatever you want about it, ala Tim Ferris & "BrainQUICKEN". There are plently of valid "incremental" critiques about the FDA. IMO, their devices and diagnostics divisions are weaker than CDER and CBER. Even those two (drug focused) divisions can be too slow moving and occasionally capricious about when they want more evidence. But their final decisions are generally pretty good, with a few exceptions. And most of those exceptions are drugs that they approved that they shouldn't have (e.g. Aduhelm) - not vice versa. Can you point at a promising drug candidate with statistically solid efficacy data that CDER or CBER has rejected? Also - note that there are approved scFVs and VHHs and mimetics - as stated in the article. Each is useful in particular situations, but none is some sort of wild medical breakthrough. There is just no evidence that any of these modalities would be attracting extraordinary investment "if only it weren't for the FDA".
- 2y ago