Research Summary

My research group works at the intersection of immunology, genome editing, synthetic biology and vectorology to improve adoptive cell therapies. Our ambition is to understand the limits of CAR  and TCR T cells using functional genomic, multidimensional single cell analysis and overcoming these challenges using novel synthetic receptors and gene editing. 

We are have been using CRISPR screens to identify key regulators of T cell exhaustion and large libraries of synthetic receptor to reprogram T cell with enhanced antitumor function. We are optimizing multiplex gene editing methods to fully reprogram and enrich for fully edited T cells.

We are also developing protein and DNA delivery methods to facilitate the manufacturing and access of gene edited T cell therapy. To study gene edited CAR T cells in immunocompetent mouse models, my lab has used directed evolution to improve AAV delivery in murine T cells. This discovery enables efficient engineering of murine T cells ex vivo and in vivo. Finally, my lab is involved in multiple collaborations to improve the clinical manufacturing of gene edited T cells including a TRAC-BCMA CAR T cell program with the UCSF Myeloma program."

 

Education

University of Bordeaux, France, B.S., 2006, Biology/Chemistry
AgroParisTech, France, Master, 2010, Bioengineering
University of Paris VII, France, Master, 2010, Genetics
University of Paris VII, France, Ph.D., 2014, Immunology - Molecular Biology
Memorial Sloan-Kettering Cancer Center, Postdoctoral, 2019, Immunotherapy

Honors & Awards

  • 2017
    Best publication of the year - Cornell/MSKCC Immunology and Microbial Pathogenesis; Eyquem et al. Nature 2017
  • 2018, 2019
    Parker Fellow Award
  • 2023
    ASGCT Outstanding New Investigator Award
  • 2024
    Pew-Stewart awards

Selected Publications

  1. Eyquem J*, Mansilla-Soto J*, Giavridis T, van D Stegen S, Hamieh M, Cunanan K, Odak A, Gönen M and Sadelain M (2017) Targeting a CAR to the TRAC locus via CRISPR/Cas9 enhances tumour rejection. Nature. PMCID: PMC5558614
  2. Mansilla-Soto J*, Eyquem J*, Feucht J, Hamieh M, Lindenbergh P, Sjöstrand M, Dobrin A, Iyer A, Li Z, Miele M,Tamzalit F, Zhao Z, Giavridis T, van der Stegen S, Garcia A, Huse M, Hendrickson R, Haubner S, Zucchetti A, Saetermoen M, Paillon N, Hivroz C, Maurin M, Rivière I and Sadelain (2022) M HLA-independent T cell receptors for targeting tumors with low antigen density. Nature Medicine. PMCID: PMC9469647. 
  3. Carnevale J, Shifrut E, Kale N, Nyberg W, Blaeschke F, Chen Y, Li Z, Bapat S, Diolaiti M, O’Leary, P, Vedova S, Belk J, Daniel B, Roth T, Bachl S, Prinzing B, Lange S, Haydar D, Luetke-Eversloh, M, Born-Bony M, Hegde B, Kogan S, Feuchtinger T, Okada H, Satpathy A, Shannon K, Gottschalk S, Eyquem J#, Krenciute G#, Ashworth A#, Marson A# (2022) RASA2 ablation in T cells boosts antigen sensitivity and long-term function. Nature. PMCID: PMC9433322 #co-corresponding.
  4. Nyberg W, Ark J, To A, Clouden S, Reeder G, Muldoon J, Chung J, Xie W, Allain V, Steinhart Z, Chang C, Talbot A, Kim S, Rosales A, Havlik P, Pimentel H, Asokan A# and Eyquem J# (2023) An evolved AAV variant enables efficient genetic engineering of murine T cells. Cell. PMCID: PMC10540678
  5. Foss D*, Muldoon J*, Nguyen D*, Carr D, Sahu S, Hunsinger J, Wyman S, Krishnappa N, Mendonsa R, Schanzer E, Shy B, Vykunta V, Allain V, Li Z, Marson A, Eyquem J# and Wilson R#. Peptide-enabled CRISPR enzyme delivery for therapeutic T cell engineering. Nature Biomedical Engineering.  2023 May 7. PMCID: PMC10129304. *contributed equally #co-corresponding.
  6. Chang C, Vykunta V, Goodman D, Muldoon J, Nyberg N, Liu C, Allain V, Rothrock A, Wang C, Marson A, Shy B# and Eyquem J#. Ultra-high efficiency T cell reprogramming at multiple loci with SEED-Selection. Nature Biotechnology (in press). And BioRxiv PMCID: PMC10871224. #co-corresponding.
  7. Nyberg W, Wang C, Ark J, Liu C, Clouden S, Qualls A, Caryotakis S, Wells E, Simon K, Garza C, Bernard PL, Lopez-Ichikawa M, Li Z, Seo J, Kimmerly G, Muldoon J, Chen PA, Li M, Liang H, Kersten K, Rosales A, Kuhn N, Ye CJ, Gardner J, Molofsky A, Ricardo-Gonzalez R, Asokan A# and Eyquem J#. Immunity (in press) #co-corresponding.

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