Aaron Ring

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Aaron Ring

Aaron Ring

@aaronmring

Associate Professor at @FredHutch Studying #cytokines, (auto)antibodies, and #cancerimmunotherapy Founder: @SimchaTx, @Seranova, @StippleBio, and @AriaxBio

Seattle, WA Katılım Ocak 2018
949 Takip Edilen9K Takipçiler
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Aaron Ring
Aaron Ring@aaronmring·
T cells do the heavy lifting when it comes to the anti-tumor action of checkpoint immunotherapy. But do antibodies play a role too? That’s the question @yile_dai looked to answer in his thesis work, out today in @Nature! 🧵below nature.com/articles/s4158…
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Justin Eyquem
Justin Eyquem@j_eyquem·
I am so excited to share our new paper in @Nature: the first programmable, site-specific integration of a large DNA payload into T cells in vivo. A single IV injection results in therapeutic levels of TRAC-targeted CAR T cells in multiple models. #Ack1" target="_blank" rel="nofollow noopener">nature.com/articles/s4158… a 🧵
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Cancer Immunoprevention Network
Cancer Immunoprevention Network@NCI_CIPNet·
🧬CIP-Net Project Spotlight: What drives the transition from MGUS to multiple myeloma? This project led by Drs. Madhav Dhodapkar @fredhutch , Richard Flavell, & Noah Palm @Yale explores how gut microbes may act as antigenic triggers for B cells, combining microbiome profiling, humanized models, and clinical studies to uncover new paths for prevention and intervention. Learn more: nci-cipnet.org/en/members/ug3…
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Mathurin Dorel
Mathurin Dorel@MathSRIsh·
@aaronmring Only a liability before a successful clinical trials, because it's an unaccounted risk factor. For drugs that passed clinical trials it's a candidate mechanism of action. It's been supposed for a while that the most effective anti cancer therapies are *because* of off target.
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Aaron Ring
Aaron Ring@aaronmring·
How specific are therapeutic monoclonal antibodies, really? In our new paper, @Yile_Dai led a collaboration with Adimab to profile 174 FDA-approved and clinical-stage mAbs against 6,172 human extracellular proteins. What we found surprised us.🧵 sciencedirect.com/science/articl…
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Aaron Ring
Aaron Ring@aaronmring·
@curcuas @lfurchtgott Most groups I know validate specificity of advanced candidates with retrogenix, etc, so the newer wave of candidates is likely cleaner.
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Leon Furchtgott
Leon Furchtgott@lfurchtgott·
We all know about small molecule polypharmacology; kind of crazy that we are only now learning that approved/late-clinical mAbs often have real off-target interactions (including pembrolizumab and lecanemab!)
Aaron Ring@aaronmring

How specific are therapeutic monoclonal antibodies, really? In our new paper, @Yile_Dai led a collaboration with Adimab to profile 174 FDA-approved and clinical-stage mAbs against 6,172 human extracellular proteins. What we found surprised us.🧵 sciencedirect.com/science/articl…

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Aaron Ring
Aaron Ring@aaronmring·
@huntry41 @Yile_Dai REAP captures some but not all of the antigens displayed in those assays. However, it has much higher throughput. Different tools for different purposes.
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Ryan Hunt
Ryan Hunt@huntry41·
@aaronmring @Yile_Dai Great work! mAbs are not always so monoclonal... How do you think this would compare to HEK cells expressing surface antigens as in the retrogenix assay? Does this platform capture a broader span of oligospecific antibodies?
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Aaron Ring
Aaron Ring@aaronmring·
@Biomaven Good eye. We wondered about this, but ultimately couldn't get convinced that pembro is that much better. Also it's an IgG4, so not a strong opsonizer (important so you don't deplete T cells). But worth further investigation I agree.
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Aaron Ring
Aaron Ring@aaronmring·
@statesdj @PearlF @Yile_Dai Sorry but it would have cost something like $12,500 to make it Open Access. Very difficult to justify that. Take it up with the publisher.
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Aaron Ring
Aaron Ring@aaronmring·
@iskander Cripto is a really interesting hit. Does make you wonder if interactions like this can explain subtle differences in efficacy between pembro and other anti-pd1s. But I'm not convinced there are big differences. Pembro is an IgG4 anyway, weak effector functions.
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alex rubinsteyn
alex rubinsteyn@iskander·
@aaronmring Would you necessarily want to abrogate binding to a TAA? Wonder how this actually plays out in vivo!
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Aaron Ring
Aaron Ring@aaronmring·
@naresh_sunkara @Yile_Dai Not in this paper, but I suspect that they may have similar levels of off-target reactivity if not pro-actively screened with platforms like retrogenix, integral molecular, etc.
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Naresh Sunkara
Naresh Sunkara@naresh_sunkara·
@aaronmring @Yile_Dai Wondering if you looked into multivalent antibodies and how their off target interactions might look like.
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Aaron Ring
Aaron Ring@aaronmring·
It was a pleasure working with the Adimab team on this study. Huge thanks to all our collaborators, especially Joseph Brouillard, Arvind Sivasubramanian, and James Geoghegan.
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Aaron Ring
Aaron Ring@aaronmring·
Bottom line: antibody/binder specificity should be measured early, not assumed. Current sequence/structure-based and AI methods like AlphaFold still do not reliably predict oligospecificity, so empirical screening remains essential.
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Keşfet

@Nature @fredhutch @Yale @j_eyquem @parkerici @UCSF @MathSRIsh @Yile_Dai