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
Important new paper from @neurosurgerynm.bsky.social and several collaborators reveals critical features of the chordoma immune landscape and lays the foundation for chordoma patients to benefit from immunotherapy advances. π§΅
academic.oup.com/neuro-oncolo...
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...
monitoring the situation as a shipment of precious chordoma samples from our biobank flys to Melbourne for our collaborators in the Firestein lab at @hudsonresearch.bsky.social βοΈ π¦πΊ
- PKMYT1 inhibitor Lunresertib
- BRG1/BRM inhibitor FHD-286
- DNA Polymerase ΞΈ 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
Positive results are celebrated, but we think sharing negative results is important too. In case helpful to anyone, here are compounds we tested in vitro in recent months which didn't show substantial activity as single agents or synergy with known active compounds:
figshare.com/authors/Chor...
Weβre hiring for a new role on our research team. It'll be an opportunity to advance interesting science, to work in a nimble and empowering environment, and, to make a tangible impact in the lives of patients in urgent need of new treatment options. www.linkedin.com/jobs/view/42...
The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma
pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/...
Weβre excited about the potential of your teamβs approach!
Interesting new challenge similar in spirit to the well known CACHE!!
For all the gains AI affords in compound design and discovery, experimental validation still remains a bottleneck. But we're making that part easy for the cancer target TBXT with a suite of biophysical, in vitro and in vivo assay capabilitiesβplus prizes for potent binders: tbxtchallenge.org
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 TBXTβand 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 TBXTβand we're offering a prize if the model identifies potent ligands: tbxtchallenge.org
π° Prof Paul Workman, our former CEO, along with his team in our Centre for Cancer Drug Discovery, have made a breakthrough that could lead to new drugs for #chordoma β a rare #BoneCancer that led to the death of his mother.
Read more in @theguardian.com ‡οΈ
www.theguardian.com/science/2025...
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
Crucial building blocks for drugging TBXT (brachyury) published by @ox.ac.uk @icr.ac.uk @uncchapelhill.bsky.social team including crystal structure, discovery of ligandable pockets, and compounds that could serve as starting points for inhibitors or degraders www.nature.com/articles/s41...
#chemsky & #compchem peeps, we need your help drugging a difficult target: TBXT (brachyury), a transcription factor critical for our disease, chordoma, and implicated in other cancers. We can offer enabling resources, free SPR analysis and now $500K+ in prizes for TBXT ligands: 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.
Two prize levels are available: $250,000 for compounds with Kd less than 300 nM and $100,000 for Kd less than 1 ΞΌM. Prizes will be awarded to up to three winners.
#chemsky & #compchem peeps, we need your help drugging a difficult target: TBXT (brachyury), a transcription factor critical for our disease, chordoma, and implicated in other cancers. We can offer enabling resources, free SPR analysis and now $500K+ in prizes for TBXT ligands: tbxtchallenge.org
We're deeply grateful to our team, our collaborators, and the many supporters who make this work possible. Stay tuned for more on each of these projects!
Finally, Tyler Vincent presented a poster describing a suite of new capabilities we've developed to enable the identification, optimization and validation of TBXT (brachyury) targeted molecules. Honored this won best poster in the Basic Science category. chordomafoundation.imgix.net/2024_CF_TBXT...
In a poster our CSO Dan Freed presented findings that chordoma cell lines exhibit striking differential sensitivity to afatinib, which is associated with interferon (IFN) signaling. Honored this won best in the Tumor Heterogeneity and Resistance category. chordomafoundation.imgix.net/CTOS_EGFRi-b...
