Huge congrats and thanks to the team behind this foundational study, particularly Caty Lee-Chang, JP Wolinsky, Victor Arrieta, Jessica Du and colleagues. We're excited to work with them and others to bring targeted immunotherapy to chordoma patients building on these new insights!

- Demonstrates tumor-specific antigen recognition by tumor-resident and peripheral T cells, suggesting potential for adoptive T cell strategies

- Suggests important roles for myeloid cells in regulating anti-tumor immunity, consistent with several prior studies but providing additional nuance
- Identifies several potential mechanisms of immune evasion in chordoma and suggests potential strategies for overcoming this evasion

In brief, it:
- Provides the largest spatial data set to date including single cell RNA-seq, TCR profiling and multiplex immunoflourescence
- Reveals three distinct patterns of immune cell composition in chordoma tumors, potentially pointing to a need for treatment strategies tailored for each

Latest negative result: Response of chordoma cell lines to treatment with the KIF18A inhibitor sovilnesib (AMG 650), as a single agent and in combination with gemcitabine figshare.com/articles/fig...

- PKMYT1 inhibitor Lunresertib
- BRG1/BRM inhibitor FHD-286
- DNA Polymerase θ inhibitor ART558
- Aurora A kinase inhibitor Alisertib
- DNA-PK inhibitor M3814
- PRMT5 inhibitor AMG 193
- GCL inhibitors, Target 831-P2 and Target S, S-408-P2

We’re excited about the potential of your team’s approach!

Congrats @ghazivakili.bsky.social! If the ability to experimentally verify your model's performance for another currently undruggable target would be helpful, we can make that easy for the transcription factor TBXT—and we're offering a prize for discovery of potent ligands: tbxtchallenge.org

Congrats @jchodera.bsky.social! If the ability to experimentally verify your models' performance for a currently undruggable target would be of interest, we can make that easy for the transcription factor TBXT—and we're offering a prize if the model identifies potent ligands: tbxtchallenge.org

So others don't have to reinvent the wheel, we've developed and offer capabilities to support TBXT drug discovery including purified protein production, SPR and various functional assays. For more info see below or get in touch: researchteam@chordoma.org www.chordomafoundation.org/researchers/...

We're excited to see how others build on these data including to compete in the TBXT Challenge (offering >$500K in prizes for more potent binders) tbxtchallenge.org

Congrats! This is an exciting approach. Any interest in giving it a try on a transcription factor? We can perform SPR for binding to the cancer associated TF TBXT and are offering prizes for compounds with <1uM Kd. tbxtchallenge.org

If you're interested in competing or have questions or suggestions, we'd love to hear from you. Please get in touch at TBXTchallenge@chordoma.org.

We hope this competition will not only accelerate discovery of urgently needed TBXT drugs, but may also serve as an opportunity to validate technologies and approaches capable of addressing other undruggable targets.

We invite companies and academic investigators to submit up to 96 compounds for free biophysical evaluation. Results will be returned confidentially and competitors retain ownership of their IP and data.