Therapeutic Product Immunogenicity Community

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  • 1.  Increase titers

    This message was posted by a user wishing to remain anonymous
    Posted 12-20-2022 09:21
    This message was posted by a user wishing to remain anonymous

    Hi Friends

    I have a question about immunogenicity.  What would be the cause of seeing increase titers of ADA when you can no longer detect the drug in subject?  This is a cell therapy depleting plasma and B cells treated with a bispecific.  There is lymphodepletion initially. 
    Any thoughts?


  • 2.  RE: Increase titers

    Community Leadership
    Posted 12-22-2022 14:26
    Thanks for sharing this discussion post! I am tagging community leaders below to assist!

    Can you provide some resources @Jochem Gokemeijer and @Yi Wen ?

    ​​

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    Stacey Axler
    Community Manager
    AAPS
    Arlington VA
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 3.  RE: Increase titers

    Posted 12-29-2022 11:54
    To anonymous:

    I can't comment about the specific modality of your drug, but consider that perhaps early in the time course, drug levels are so high so as to interfere with the ADA assay, such that ADA are not detected or detected at a lower level. Later in the time course, when drug levels have gone down, the ADA can be fully detected and thus give the impression of increasing titers. I have seen this a number of times.

    John Kamerud

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    John Kamerud Ph.D.
    Director
    Pfizer Inc
    Andover MA
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 4.  RE: Increase titers

    Posted 01-02-2023 11:18
    One possible reason for the increase in ADA is that the treatment did not sufficiently deplete the antigen specific T and B cell clones responding to your biological.  An indirect example of this result can be found in the Lilly paper published by Wendy Komocsar et al. 2015.  Preclinical treatment of cynos with an anti-BAFF monoclonal antibody reduced circulating B cells and the size of splenic germinal centers, but did not inhibit antibody responses to tetanus toxoid or KLH challenge.  Unfortunately, ADA to tabalumab itself was not assessed in this study due to assay interference from circulating drug, and I am unaware of clinical immunogenicity results that may have been obtained during trials with this mAB. If there was ADA detected in the latter, that information would more directly address your question.

    Dan Wierda
    R&D Director
    Xeno Diagnostics
    Indianapolis, IN
    [email protected]

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    Daniel Wierda PhD
    Immunotoxicologist
    Xeno Diagnostics
    Indianapolis IN
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message


  • 5.  RE: Increase titers

    Posted 01-11-2023 09:30
    have you considered drug interference in the ADA assay as a possible explanation? When drug clears, higher levels of ADA might be detected?

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    Per Holse Mygind
    Director, Clinical Biomarkers & Immunogenicity
    Ascendis Pharma
    Hellerup
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
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    Original Message