5 ms·

Nanobodies have been around for decades, and there are reasons why they're not part of any drugs - half life is bonkers terrible (months for regular mammalian a

Nanobodies have been around for decades, and there are reasons why they're not part of any drugs - half life is bonkers terrible (months for regular mammalian antibodies vs. hours) + non zero risk of immune reactions towards these foreign (to our genome) proteins. Source: PhD (partly) in antibody engineering

dnautics 6y ago
I came here to same more or less the same thing. They are, however (potentially) a good analytical tool.
- ramraj07 6y ago
  Also probably a good imaging agent, but then that's like the consolation prize for every "promising" targeting approach who's "only" flaw is a shitty half life, so no end to competition!
zasz 6y ago
It does say in the article it could be a helpful treatment for people who have tested positive for covid. Do you think that's just hype, or could it actually be helpful?
- ramraj07 6y ago
  Seems boilerplate "could be helpful to cure xxx" statements written in press releases and grants for most research findings; neutralizing antibodies do seem to help in mitigating worse outcomes (among others Lily sells a concoction) but even when they have good half lives it looks like the neutralizers don't do too much; there's no benefit I can see for something with orders of magnitude lower half life still.
- colechristensen 6y ago
  “Could be” in this context is more like “hasn’t been conclusively proven impossible”. Unless somebody is taking about human trials it is exploratory and not worth getting anybody’s hopes up unless your hopes involve grant money and publishing papers.
- benrapscallion 6y ago
  Mostly hype.
dbcooper 6y ago
Absolutely right, Pfizer has failed on those as drug candidates for the last 20 years.
curiousboon 6y ago
This is cheaper to produce and can be take more regularly than monoclonal antibodies. The more options the better!
- ramraj07 6y ago
  The only places where short half life proteins have been useful is if you're delivering toxic substances and you don't want any off target effects (see BiTes - https://en.m.wikipedia.org/wiki/Bi-specific_T-cell_engager https://en.m.wikipedia.org/wiki/Bi-specific_T-cell_engager ) the technology behind the targeted becomes less relevant if you don't care about the half life. You can make antibody fragments that are only slightly larger that are still fine.
zepin 6y ago
> and there are reasons why they're not part of any drugs Caplacizumab (Cablivi®) is a Nanobody (2 VH units linked together) approved by the EMA since 2018 (and by the FDA since 2019).
- ramraj07 6y ago
  Touche, there do seem to be approvals. I'll edit my post.
- Cthulhu_ 6y ago
  One example of a very new drug; do you have any others? Any studies on its efficacy and side effects?
  - FrojoS 6y ago
    It’s a bit unfair to ask the parent to do this legwork. The fact that it got approved implies that it is effective and that side effects are rare and/or relatively minor. Edit: From the phase II trial: “ Adverse events overall were similar between groups, with the exception of bleeding, which occurred more often with the immunoglobulin treatment (54% versus 38%). The two participants who died were both in the placebo group.” https://www.medpagetoday.com/Cardiology/VenousThrombosis/56154 https://www.medpagetoday.com/Cardiology/VenousThrombosis/561...
- AstralStorm 6y ago
  Mind you this is used for TTP and thrombosis, where short lifetime is a benefit. You want to remove the clotting factor now, not forever. (We have drugs for that too.)
  - est31 6y ago
    Short lifetime can be a benefit for anti-Covid medication too. An antibody could cross react with a vaccine and hamper the immune system response, preventing it from launching a proper reaction and creating proper immunity. You don't want the person having to wait for weeks while being vulnerable until they can get a vaccine after a successful therapy with antibodies. But of course, distribution is a headache.
lifeplusplus 6y ago
isn't the point to reduce severity... in icu with ventilator vs little cough? if viral load annihilated the immune response would be light and less damage to organs.

dnautics 6y ago

I came here to same more or less the same thing. They are, however (potentially) a good analytical tool.

ramraj07 6y ago
Also probably a good imaging agent, but then that's like the consolation prize for every "promising" targeting approach who's "only" flaw is a shitty half life, so no end to competition!

zasz 6y ago

It does say in the article it could be a helpful treatment for people who have tested positive for covid. Do you think that's just hype, or could it actually be helpful?

ramraj07 6y ago
Seems boilerplate "could be helpful to cure xxx" statements written in press releases and grants for most research findings; neutralizing antibodies do seem to help in mitigating worse outcomes (among others Lily sells a concoction) but even when they have good half lives it looks like the neutralizers don't do too much; there's no benefit I can see for something with orders of magnitude lower half life still.
colechristensen 6y ago
“Could be” in this context is more like “hasn’t been conclusively proven impossible”. Unless somebody is taking about human trials it is exploratory and not worth getting anybody’s hopes up unless your hopes involve grant money and publishing papers.
benrapscallion 6y ago
Mostly hype.

dbcooper 6y ago

Absolutely right, Pfizer has failed on those as drug candidates for the last 20 years.

curiousboon 6y ago

This is cheaper to produce and can be take more regularly than monoclonal antibodies. The more options the better!

ramraj07 6y ago
The only places where short half life proteins have been useful is if you're delivering toxic substances and you don't want any off target effects (see BiTes - https://en.m.wikipedia.org/wiki/Bi-specific_T-cell_engager https://en.m.wikipedia.org/wiki/Bi-specific_T-cell_engager ) the technology behind the targeted becomes less relevant if you don't care about the half life. You can make antibody fragments that are only slightly larger that are still fine.

zepin 6y ago

> and there are reasons why they're not part of any drugs Caplacizumab (Cablivi®) is a Nanobody (2 VH units linked together) approved by the EMA since 2018 (and by the FDA since 2019).

ramraj07 6y ago
Touche, there do seem to be approvals. I'll edit my post.
Cthulhu_ 6y ago
One example of a very new drug; do you have any others? Any studies on its efficacy and side effects?
- FrojoS 6y ago
  It’s a bit unfair to ask the parent to do this legwork. The fact that it got approved implies that it is effective and that side effects are rare and/or relatively minor. Edit: From the phase II trial: “ Adverse events overall were similar between groups, with the exception of bleeding, which occurred more often with the immunoglobulin treatment (54% versus 38%). The two participants who died were both in the placebo group.” https://www.medpagetoday.com/Cardiology/VenousThrombosis/56154 https://www.medpagetoday.com/Cardiology/VenousThrombosis/561...
AstralStorm 6y ago
Mind you this is used for TTP and thrombosis, where short lifetime is a benefit. You want to remove the clotting factor now, not forever. (We have drugs for that too.)
- est31 6y ago
  Short lifetime can be a benefit for anti-Covid medication too. An antibody could cross react with a vaccine and hamper the immune system response, preventing it from launching a proper reaction and creating proper immunity. You don't want the person having to wait for weeks while being vulnerable until they can get a vaccine after a successful therapy with antibodies. But of course, distribution is a headache.

lifeplusplus 6y ago

isn't the point to reduce severity... in icu with ventilator vs little cough? if viral load annihilated the immune response would be light and less damage to organs.