Thank you for sharing this, Johanna. Advanced therapies are challenging our understanding of immunogenicity to biologics in the sense that immune-related toxicities are mixed up with adverse events mediated by ADA. Fully agree in that CRS mediated neurotoxity is rather linked to the MoA of CART but not mediated by anti-CAR T antibodies. In my opinion, we should continue to emphasize the relevance of a risk assessment to interpret clinical outcomes.
Best,
Laura
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Laura Salazar-Fontana
Principal
LAIZ Reg Science Consulting
Lausanne
[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:
Sent: 04-11-2024 14:29
From: Johanna Mora
Subject: ADA and AEs for CT
Hi Community,
If you have been doing IMG analysis for biotherapeutics, you may have worked in some outputs that consider ADA impact on safety, and as per Shakar we look at "infusion reactions and anaphylaxis (6,7) as well as immune complex-mediated diseases.." in addition, depending on the mechanism of action you may consider thromboembolism or others. In my review of some documents related to cell therapies, I have seen iiNTs (identified by investigators as Neurotoxicity) among the AEs looked into for such outputs. I don't see how an ADA to CT would have caused NT, can someone helped me? If not, is this just a bad practice started elsewhere that we should stop.
CRS is a bit tricky, b/c the CT itself is associated with it, not the ADA response, but I am hesitant to push back on removing it.
Pls share your thoughts!
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Johanna Mora Ph.D.
Bristol-Myers Squibb
Princeton NJ
[email protected]
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