Sylvain Simon

Fred Hutchinson Cancer Center Fred Hutch is dedicated to the elimination of cancer and related diseases as causes of human suffering and death.

If interested, please follow the job post below and/or reach out directly to me with your personal statement that includes your research interests and a CV. social.icims.com/viewjob/pl17...

The candidate should have a PhD and/or MD in immunology, cancer biology or bioengineering and experience in wet lab research. Prior experience in immunology and T cell biology, T cell signaling and synthetic biology is highly desirable.

We are hiring! We have a postdoc position opened @fredhutch.org to join our team to design next gen cellular therapies for cancer. Heavy focus on T cell signaling and understanding how synthetic receptors instruct T cells to fight cancer.

Targeting peptide-MHC complexes with designed T cell receptors and antibodies Class I major histocompatibility complexes (MHCs), expressed on the surface of all nucleated cells, present peptides derived from intracellular proteins for surveillance by T cells. The precise recogn...

Hey @jamieheather.bsky.social what do you think of this?

www.biorxiv.org/content/10.1...

TIRTL-seq: deep, quantitative and affordable paired TCR repertoire sequencing - Nature Methods TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.

Two complementary studies from our group out today: a therapeutic peptide vaccine trial for fibrolamellar carcinoma (FLC) & TIRTL-Seq, our robust method for deep quantitative paired TCR sequencing a🧵w/ @markyarchoan.bsky.social & @pogorely.bsky.social www.nature.com/articles/s41...

Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy @natcancer.nature.com
www.nature.com/articles/s43...

We are using principles from fundamental T-cell biology and synthetic biology tools to design next-generation T cell therapies for cancer. The lab is now open and hiring — if you’re interested in engineering immune cells to combat cancer and tumor heterogeneity, please reach out!

Excited to announce that I’ve recently transitioned into an Assistant Professor role in the Division of Translational Science and Therapeutics @Fred Hutch.

Check out one of our latest stories about combining our non viral knock-in strategy with integrases for an efficient, targeted integration of transgenes >8kb in human T cells!

‘One-pot’ PASTA: programmable and site specific transgene addition - all in just one reaction 🫕

Modulating AP-1 enables CAR-T cells to establish an intratumoral PD-1+ Tcf1+ stem-like reservoir and overcomes resistance to PD-1 axis blockade
www.biorxiv.org/content/10.1...

Modulating AP-1 enables CAR-T cells to establish an intratumoral PD-1+Tcf1+ stem-like reservoir and overcomes resistance to PD-1 axis blockade https://www.biorxiv.org/content/10.1101/2025.04.10.648245v1

With these advances, we hope to see the Bi-ChTCRs move to the clinic, hoping to generate long-lasting responses and prevent relapses in patients.
@fredhutch.bsky.social @natureportfolio.nature.com @naturecancer.bsky.social
#CancerResearch #Immunotherapy #TCellTherapy #BiChTCR #SyntheticImmunity

Finally, we demonstrated that eliminating the endogenous TCR chains – here using base editing – was essential to maximize the expression level and therefore antigen sensitivity of this emerging class of HLA-independent receptors, and should be taken into consideration for clinical applications.

While bispecific CARs are often compromised for antigen binding and for signaling, we showed that Bi-ChTCRs maintained exquisite antigen sensitivity! We think this is due to the multimeric assembly of the TCR where TCR chains need to pair for expression at the membrane yet function independently!

The Bi-ChTCR platform was resilient as we were able to extend our findings initially targeting CD19 and CD22 antigens to Bi-ChTCRs targeting multiple pairs of Multiple Myeloma antigens.

T cells equipped with Bi-ChTCRs demonstrated “true” bispecificity in vitro and could eliminate tumors heterogenous for antigen expression and antigen levels in mouse models outperforming bispecific CARs or a mixture of monospecific CAR products.

These bispecific Chimeric TCRs recapitulated the TCR structure pairing with CD3 subunits, formed bull’s eye immune synapses and demonstrated potent TCR-like proximal signaling leading to superior sensitivity in comparison to classical CAR designs and previously described HLA-independent receptors.

Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy Nature Cancer - Simon, Bugos and colleagues report the design and characterization of monospecific and bispecific synthetic chimeric T cell receptors, conferring increased antigen sensitivity and...

Exciting news! Our latest manuscript is out! Really happy to report on the development of synthetic chimeric TCRs with enhanced antigen sensitivity and capable of bispecificity to successfully overcome tumor heterogeneity in pre-clinical models.

Check it out: rdcu.be/edRwJ

With these advances, we hope to see the Bi-ChTCRs move to the clinic, hoping to generate long-lasting responses and prevent relapses in cancer patients.

@fredhutch.bsky.social
#CancerResearch #Immunotherapy #TCellTherapy #Bi-ChTCR #SyntheticImmunity

Finally, we demonstrated that eliminating the endogenous TCR chains – here using base editing – was essential to maximize the expression level and therefore antigen sensitivity of this emerging class of HLA-independent receptors, and should be taken into consideration for clinical applications.

While bispecific CARs are often compromised for antigen binding and for signaling, Bi-ChTCRs maintained exquisite antigen sensitivity! We believe this is due to the multimeric assembly of the TCR complex where each TCR chain need to pair for expression at the membrane yet function independently!

Furthermore, the Bi-ChTCR platform was resilient as we were able to extend our findings initially targeting CD19 and CD22 antigens to Bi-ChTCRs targeting multiple pairs of Multiple Myeloma antigens.

T cells equipped with Bi-ChTCRs demonstrated “true” bispecificity in vitro and could eliminate tumors heterogenous for antigen expression and antigen levels in mouse models outperforming bispecific CARs or a mixture of monospecific CAR products.

These bispecific ChTCRs recapitulated the TCR structure pairing with CD3 subunits, formed bull’s eye immune synapses and demonstrated potent TCR-like proximal signaling leading to superior antigen sensitivity in comparison to classical CAR designs and previously described HLA-independent receptors.

CytoNorm 2.0: A flexible normalization framework for cytometry data without requiring dedicated controls Cytometry is a single cell, high-dimensional, high-throughput technique that is being applied across a range of disciplines. However, many elements alongside the data acquisition process might give r...

Flow cytometry batch effect correction without requiring normalization controls 🤩
onlinelibrary.wiley.com/doi/full/10....

YouTube video by Association of American Universities Facilities and Administrative (F&A) Costs Explainer

Make sure you, your trainees, and anyone else who might listen to you understands what "indirects" actually are, how they are established, and what Universities contribute. H/T @rodallab.bsky.social

Please share widely!

www.youtube.com/watch?v=yxTD...

👀 🤯