August 8th, 2016: Understanding and Remembrance Day for Severe Myalgic Encephalomyelitis
Jody Smith joins with other ME voices in honor of Understanding and Remembrance Day for Severe Myalgic Encephalomyelitis.
Discuss the article on the Forums.

Yet another anti-CD20 mAb in the works: Ocaratuzumab

Discussion in 'Rituximab: News and Research' started by leokitten, May 18, 2015.

  1. leokitten

    leokitten Senior Member

    Messages:
    580
    Likes:
    1,876
    Maryland
    In addition to the anti-CD20 type I mAbs Rituximab and Ofatumumab and the glycoengineered type II mAb Obinutuzumab, now there is also the novel Fc-engineered Ocaratuzumab http://en.m.wikipedia.org/wiki/Ocaratuzumab.

    It says that in addition to targeting B-cell cancers it's also being investigated to treat autoimmune conditions such as RA:

    Low Doses Of Ocaratuzumab, A Fc- And Fab-Engineered Anti-CD20 Antibody, Result In Rapid And Sustained Depletion Of Circulating B-Cells In Rheumatoid Arthritis Patients.
     
    Last edited: May 18, 2015
    Sancar, Scarecrow, alex3619 and 6 others like this.
  2. deleder2k

    deleder2k Senior Member

    Messages:
    1,104
    Likes:
    4,744
    Is this a more efficient drug in killing memory B-cells than RTX? I'd love to hear your take on this professor @Jonathan Edwards.
     
  3. leokitten

    leokitten Senior Member

    Messages:
    580
    Likes:
    1,876
    Maryland
    Yes:
     
    deleder2k likes this.
  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,219
    Likes:
    31,680
    I don't know the details about this one. It is almost certainly better in some respects, otherwise a company would not be progressing it. The claims made may be a bit misleading though. Rituximab probably produces complete B cell depletion in most people for three months at a tenth the standard dose and maybe even less. the problem is that 'the majority of patients' is not reliable enough. Moreover 3 months is probably too short. Improvement has barely kicked by then. Fluge and Mella's idea of keeping B cells low for about two years makes a lot of sense. So although this new one is likely to be stronger, it is a bit hyped.

    The affinity for CD20 may not be of any relevance. As long as it binds reasonably tightly an antibody will mediate lysis. What we know about rituximab is that it turned out to bind to a particularly good target antigen (CD20) for no predictable reason (nobody knew much about CD20 at the time) and also to an epitope that mediated good killing. An antibody that binds another epitope might not work as well. However, it looks as if this new one is at least better at killing in ADCC. That is not the only mechanism of killing but it is the one I have thought of as giving better risk/benefit (complement lysis can produce unwanted effects). They talk about it being better for the low affinity polymorphism of FcRIIIa but to be honest the evidence for this being critical in autoimmune disease treatment was unconvincing.

    Nevertheless, they are bound to have hyped whatever claims they have but it is still likely to be a useful advance.

    What we cannot tell from any of this is whether or not it will kill memory N cells hidden away in protected environments full of death inhibitors. It may be that however fancy you make an anti-CD20 you do not actually get any better result if the residual problem for rituximab is hidden cells rather than potency. However, common sense would suggest that at least there is a chance you can get at them with higher killing efficiency.
     
    Sancar, Sidereal, Valentijn and 3 others like this.
  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,219
    Likes:
    31,680
    Actually looking at the abstract (which is just a meeting presentation, not a paper) it seems that they did not necessarily get complete (98%) depletion and more importantly B cells started coming back at 7 days. This is completely useless therapeutically. When Eisenberg used rituximab in lupus at very low dose I think he got at least as much depletion as that. It also looks from the way it is written that the authors do not know a lot about the pharmacodynamics of B cell depletion in RA. Still it is an interesting new variant.
     
  6. lansbergen

    lansbergen Senior Member

    Messages:
    2,478
    Likes:
    2,671
    N cells
    http://www.copewithcytokines.de/cope.cgi?key=N cells
    http://en.wikipedia.org/wiki/Neurotensin
    http://www.copewithcytokines.de/cope.cgi?key=N cells
     
  7. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,613
    Likes:
    12,428
    South Australia
    Rituximab is a big seller (revenue in the billions of dollars per year), and is either no longer protected by patents, or going off patent in the next few years.

    There is definitely a market, even if it is similarly, rather than more effective than Ritxuimab. But safety and efficacy for specific conditions still needs to be done before approval.
     
  8. lansbergen

    lansbergen Senior Member

    Messages:
    2,478
    Likes:
    2,671
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488904/
    NT is neurotensin
     
  9. deleder2k

    deleder2k Senior Member

    Messages:
    1,104
    Likes:
    4,744
    @Jonathan Edwards, thank you for your answers.

    I didn't get that either.

    And then

    Seven days? I thought with RTX B-cells wouldn't be produced for at least a few months.


    So what do we really need? Some drug that kills that hide in lymph nodes and other places?

    I wonder how far they've come with Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies. This one is a few years old.
     
  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,219
    Likes:
    31,680
    Sorry about the N cell typo - I see that N is next to B on the keyboard! Interesting to know that N cells exist though.

    I am optimistic that all this activity will produce better B cell depleting agents. Which one is going to be best may be hard to tell just yet but I would hope there will be a quantum leap in therapeutic benefit in the next couple of years.

    I think B cells come back after a few days if the dose given is all mopped up by cells in that time and any cells not yet killed in lymph nodes or marrow can start coming out again. Getting rid of cells actually in the circulation is easy because they are a tiny proportion of the whole and are awash with drug. It looks to me as if a realistic dose for this new drug might be 50-100mg rather than 500mg.
     
    deleder2k likes this.
  11. deleder2k

    deleder2k Senior Member

    Messages:
    1,104
    Likes:
    4,744
    I didn't realise there was a typo, hehe. I hadn't heard about N-cells before though. I learn something new everyday on this forum.

    http://www.invivogen.com/anti-hcd20-higg1fut

    Perhaps this will cure me once. Who knows!
     

See more popular forum discussions.

Share This Page