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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

That’s a wrap for the day on antibody drug conjugates at the @mitkochinstitute.bsky.social ! Awesome course on these complicated and exciting molecules (and their relatives)! Lots more exciting anti-cancer science to come 💊 #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Modifying chemistry of ADCs, such as through adding polar groups to increase lipophilicity is a separate approach that helps improve ADC pharmacokinetics and tolerability @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Different toxicities can appear with better linkers- indicating a need to better understand the biology of ADCs, as well as improve in other ways to mitigate this toxicity @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

With an unstable linker, side effects mimic those of non-ab mediated systemic treatment with the same drug and safe dosage levels are no different. Stable linkers improve this, safely enabling higher payload doses. TLDR; linker is critical! @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Michael Seganish closes out the day discussing what happens when an ADC payloads detaches, even when it’s supposed to, and gets into circulation instead of into its target cell. Spoiler alert: toxic side effects @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

A new challenge: what to do after development of resistance to ADC treatment- re-treating with a new ADC often doesn’t work. More to learn! #KIsymposium @mitkochinstitute.bsky.social

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

What biomarkers predict success on ADCs? 2 AI models work together to automate image analysis and identify tumor cells that are targetable by ADCs, defining a signature that can be used to identify strong patient candidates. @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Puja Sapra brings perspective on the evolution of the ADC field: much learned and much to be done in terms of improving targets, understanding why different ADCs work differently, and deriving novel combos for future use. @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

More quantitative systems modeling in the Thurber lab has helped identify these balances given lots of data- aiding in figure design of these molecules, which don’t follow the same principles as other drugs. #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

One approach: lower drug to antibody ratio gets drug into the tissue more efficiently and improves efficacy overall while lowering concerns about toxicity. Second: Use more of a lower potency payload that's more tolerable- It's all about balance. #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Mouse models have taught lessons about how ADCs biodistribute + enter tissue which isn't always well- a challenge to be overcome. Higher/more frequent dosages don't always fix this, since there's a risk of toxicity with higher payload. #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Challenges remain: most ADCs don't reach the tumor and still circulate (though don't bind), and what does often doesn't distribute through the tumor well. How do we think about fixing?

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Greg Thurber starts session 3 with perspective on the trajectory of ADCs in the clinic & in research- there's been a steady increase in approved ADC molecules for clinical use since early 2000s! @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Challenges remain: most ADCs don't reach the tumor and still circulate (though don't bind), and what does often doesn't distribute through the tumor well. How do we think about fixing? @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

With a smaller size and shorter half-life in the body than ADCs, they can get into tumors better, clear out of normal tissues more easily, while still being potent and specific @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Daša Lipovšek expanding today's discussion to include miniprotein radioconjugates, which link target-binding proteins with radioisotopes that can kill cells or be detected with imaging devices. This facilitates greater targeting and functionality. @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Jeremiah Johnson's antibody-bottlebrush conjugates aim to enable loading more drug onto ADCs using hydrophilic sidechain linkers that stabilize more, larger, & combos of payloads. This opens doors to more options for ADC design across more contexts @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Dane Wittrup's lab is innovating ADCs by designing linker-less ADCs, which can enable release of payloads that cells can then take up over time- enabling better and potentially more potent targeting @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

The Boyer lab optimized physically expanding cells and then imaging them in a 96-well plate format- reaching the resolution of higher-power instruments without the cost. Now ADCs at work can be observed! @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Kicking off session 2 is Laurie Boyer, discussing how to visualize how molecules (like ADCs) are traveling into and around cells. Regular light microscopy isn't sufficient and more complicated super-resolution microscopes are expensive and hard to use.

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Last in Session 1: Timothy Lowinger discusses targeting immune pathways! STING agonism activates innate immunity, but it's important and difficult to deliver this only to tumor lesions. ADCs can bring the drug directly to the tumor microenvironment @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

So much can be done with these models combining in vitro, mouse, and clinical studies- understanding bystander effects of ADCs, studying off-target toxicities, and even creating computer-simulated trials to predict what would happen in patient cohorts. @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Alison Betts: With the promise of ADCs comes a need to better understand their mechanisms + toxicities. Quantitative Systems Pharmacology modeling uses applied math to study data from ADC trials, aiding in the design of new & improved versions. @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

It makes sense that this therapy might work in HER2+ patients. But a big question today- why do these also show efficacy in HER2-low (even ultra-low!) patients? Exciting results and lots to learn still... @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Next in session 1: Gerold Meinhardt with clinical data on Trastuzumab Deruxtecan, a HER2 ADC with great efficacy for breast cancer patients in a variety of contexts, including patients that have already been treated with other agents @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Lots of opportunities to use ADCs in the clinic: changing linkers, using different payloads, & modifying targets can open doors for a variety of diseases and contexts- sometimes through unexpected mechanisms that can be understood and studied further! @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

One challenge: antibodies usually sit on the cell surface- this can be OK! But, how to get more effectively drugs into the cells? Bispecifics can help- two targets can be better than one. Or, non-antibodies that bind receptors (for example) can also deliver drugs. @mitkochinstitute.bsky.social

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Now, Peter Senter discussing challenges and progress in antibody drug conjugates for cancer- tricky in terms of design, potency, toxicity, etc. However, ADCs have already led to huge improvements, such as in Hodgkin's lyphoma and urothelial cancer. #KIsymposium @mitkochinstitute.bsky.social

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

2)"Click to release"- delivering chemotherapy (as an example) that is 'caged' in a protodrug that only activates (using click chemistry) to a specific location in the body (lowering side effects, increasing specificity, etc) @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Two more examples of click chemistry doing important things in cancer: 1) Using bioorthogonal chemistry to modify "off the shelf" gdT-cells to an antibody-cell conjugate for delivering to patients quicker & less expensively than conventional CAR-Ts @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Now, a reminder that the chemistry necessary to link antibodies and drugs to make a pure compound for treating patients is complicated and difficult, and has taken decades of study to get right. Enter bioorthogonal chemistry for control + specificity! @mitkochinstitute.bsky.social #KIsymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

An awesome overview of "Click Chemistry"- developed & optimized by Dr. Bertozzi (and co-Nobelians) to label cell surface glycans. These findings led to important discoveries, and also has important applications in drug design (such as antibody-drug conjugates!) @mitkochinstitute.bsky.social

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

First, our keynote speaker @carolynbertozzi.bskyverified.social (Nobel Laureate!) introducing bioorthogonal chemistry: reactions that can occur within a living cell, with all its physiological constraints, without interfering with biology @mitkochinstitute.bsky.social #KISymposium

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/06/2025

Live posting today from the @mitkochinstitute.bsky.social annual symposium on Antibody Drug Conjugates #KISymposium. Excited for the amazing lineup of speakers!

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Reposted by Meaghan McGeary, PhD

Ludwig Cancer Research @ludwigcancer.bsky.social · 11/06/2025

We recently attended the Ludwig @mit.edu retreat and caught up with many of our colleagues there. Here, founding Director, Ludwig Professor and giant of cancer research Robert Weinberg reflects on his scientific fascinations and career. youtu.be/UEDP2_RA6MI #CanSky #OncoSky

youtu.be

Robert Weinberg, Ludwig MIT

YouTube video by Ludwig Cancer Research

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Reposted by Meaghan McGeary, PhD

MIT Koch Institute @mitkochinstitute.bsky.social · 10/06/2025

“It’s not justifying the research—it’s justifying spending money on the research.” This spring, Koch Institute postdoc Meaghan McGeary took that message to Capitol Hill during AACR Hill Day, urging policymakers to sustain federal funding for cancer research. buff.ly/EgnUNzq

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

Grateful for this experience, for the colleagues I got to work with today, and for @theaacr.bsky.social including me in this year’s group, and organizing all these meetings. I have a lot of hope for the progress we can make on cancer and it was an honor to voice this on Capitol Hill today!

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

I hope sharing our stories helped convince our senators + reps of the need to #FundNIH to keep the US research space competitive, keep cancer research going, and continue training brilliant scientists! The cancer problem isn’t getting easier- and we can’t let up on it now!

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

We asked our Congressional reps + senators across many states, on both sides of the aisle, to do everything they can to increase funding for NIH and NCI so that we can keep this work going and capitalize on the breakthroughs that are happening to extend and improve cancer patients’ lives

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

Cancer is a bi-partisan disease- it has impacted nearly every family, friend group, workplace. We are learning more every day about how to combat it in its many forms- and this depends on funding the expensive but important research my colleagues and I do across the country

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

Today I visited Capitol Hill with @theaacr.bsky.social and other early-career cancer researchers to advocate for increasing funding to NIH and NCI, and to share the impact of recent measures to cut federal spending on research. It was exciting and empowering, and I learned so much. 🧵

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

Grateful for this experience, for the colleagues I got to work with today, and for @AACR including me in this year’s group, and organizing all these meetings. I have a lot of hope for the progress we can make on cancer and it was an honor to voice this on Capitol Hill today!

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

We asked our Congressional reps across many states, on both sides of the aisle, to do everything they can to increase funding for NIH and NCI so that we can keep this work going and capitalize on the breakthroughs that are happening to extend and improve cancer patients’ lives

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 27/02/2025

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 26/02/2025

Last meeting- grateful for the time in @nadler.house.gov office to discuss what loss of cancer research funding means for NYC and the country @aacr_cancerresearch #FundNIH #AACRontheHill

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 26/02/2025

Thanks to @whipkclark.bsky.social office for meeting with us to hear how NIH funding cuts hurt MA innovation + cancer researchers! #FundNIH #AACRontheHill @AACR @Pederfizzo

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Meaghan McGeary, PhD @mk-mcg5.bsky.social · 26/02/2025

Grateful to @SenSchumer office for hearing our concerns about loss of funding for cancer research #FundNIH @theaacr.bsky.social

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