Lightnews — Scholar-powered news

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Learn more at biomlsociety.org/challenge

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Huge shoutout to everyone that helped put on this event :)
Alex Abel, Aaron Feller, Amanda Cifuentes Rieffer, Phillip Woolley, Daryl Barth, Tynan Gardner , Wesley Wierson, Andrew Ellington, & Edward Marcotte (@edwardmarcotte.bsky.social)

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

We’re hoping to elucidate and share the trends in method choices to help our community hone in on standard practices for successful protein design :)

Stay tuned!

1 2

Clay Kosonocky @kosonocky.bsky.social · Sep 2

The full data release, scores, and analysis will be coming soon. We wish we could share all of the stats right now but we think it’s best if we release everything all at once when the publication hits preprint (hopefully in October!)

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Huge congrats to the winners! This is an absolutely mind-blowing feat and we can’t believe that designs from this competition worked so well. Each of the four winners will be given a 3D print of their winning binder, some stylish LEAH Labs swag, and, of course, bragging rights!

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

We’re also giving a second award to the team with the highest success rate of submitted sequences in the Round 1 screen. This team was Nucleate UK with a whopping 38% hit rate, with the runnerups being BindingIllini (15%) and Furman Lab (11%)

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Each design in the top ten succeeded at some aspect of T cell biology, but a few were successful in all of them! The teams with the top three designs were the Perez Lab Gators, Amigo Acids, and the Schoeder Lab. Each of these teams will be given an award 🥇

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Round 2 (Individual Functional Assays)

The ten best performing sequences from Round 1 were selected to move on to a series of individual assays measuring many aspects of T cell biology including cytotoxicity against CD20+ tumors, cytokine release, proliferation, and expansion

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

This approach hijacks a necessary but not sufficient behavior of functional T cells—proliferation—to identify which binders engaged the antigen, signaled through their CAR, and became overrepresented at the population level

1 1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Round 1 (High-Throughput Screen)

The 12,000 CAR-T cell constructs were tested in a high-throughput pooled screen to measure how well the binders drove CAR-T cell proliferation in the presence of the target antigen CD20 compared to a control

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

The binders functioned in the context of CAR-T cells, serving as the binding domain that helps the CAR-T recognize the cancer antigen CD20. To validate them, we did two rounds of testing:

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

This was only possible thanks to LEAH Labs' high-throughput T cell engineering screen, DNA synthesis from
@twistbioscience.com, reagents from Lonza Group, ScaleReady, and VWR, and additional funding from the Center for Systems & Synthetic Biology at UT Austin

1 1 1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

We had 28 teams with competitors from 40 different countries design and submit a total of *12,000* peptide binders. All of the designs and methods, both in silico and in vitro, will be made public, and all parties agreed that no IP will be claimed to help further open science

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

The methods used by scientists from *all over the world* resulted in antigen binders that plausibly act as cancer therapeutics. We can’t get over how cool this is!

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

Rather than test for just binding affinity, we tested these binders directly in the therapeutic modality to see how well AI protein design tools work towards a real-world scenario that could one day accelerate cell therapy prescription to days or weeks, rather than years

1

Clay Kosonocky @kosonocky.bsky.social · Sep 2

🚨The Bits to Binders Competition has concluded!🧬

One year ago we gathered scientists from around the world to design and submit protein binders that cause immune cells to target and eliminate CD20+ tumors

Spoiler: They work!

1 2 5