Sébastien Wälchli
- Senior Scientist; PhD
- +47 22 78 13 16
Group leader
Education:
2016 |
Present |
Senior scientist (group leader-OUS leader training 2019) |
Section for Cellular Therapy, Radiumhospitalet, Oslo |
2013 |
2016 |
Senior scientist (project leader) |
Sections for Cancer Immunology and Cellular Therapy, Radiumhospitalet, Oslo |
2007 |
2013 |
Scientist |
Dept of Immunology, IKF, Radiumhospitalet, Oslo |
2003 |
2007 |
Postdoc |
Dept of Biochemistry, IKF, Radiumhospitalet, Oslo |
2002 |
2003 |
Visiting scientist |
Medical school of Geneva, Geneva, Switzerland |
1998 |
2002 |
PhD student |
Serono Pharmaceutical Research Institute (Hooft), Geneva, Switzerland |
Research interests/projects:
SW co-leads the translational research lab at the section for Cellular therapy, OUS, a newly established pre-clinical entity directly connected to the immunomonitoring unit. SW leads the molecular biology of the T-cell receptor (TCR) and the Chimeric Antigen Receptor (CAR) development platforms. The TCR platform has led to the filling of numerous patents, the establishment of a biotech (Zelluna Immuntherapy AS, 2016) and the first TCR tested in human in Norway (ClinicalTrials.gov Identifier: NCT03431311). The CAR platform has completed the pre-clinical development of 2 candidates and is working on around 15 new constructs, most of them directed against solid tumours. Advanced universal therapeutic solutions are also in our pipeline (3 patents), and different innovative tools in the immunotherapeutic field (vaccination, effector cell improvement, etc.). More info here: www.linkedin.com/in/sebastw |
Awards
- OvaCure Award at the OvaCure Innovation Challenge 2020
- Inven2 Innovation award 2014: "A universal killer-T cell for personalized medicine"
- Top poster Award at CIMT (Association of Cancer Immunotherapy) in Mainz (Germany) 2012: "It takes two to tango: MHC-I and Invariant chain in harmony"
- Inven2 Innovation award 2011: "A novel method to produce soluble TcR"
Publications 2024
CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies
Oncoimmunology, 13 (1), 2362454
DOI 10.1080/2162402X.2024.2362454, PubMed 38846084
Efficient CAR T cell targeting of the CA125 extracellular repeat domain of MUC16
J Immunother Cancer, 12 (4)
DOI 10.1136/jitc-2023-008179, PubMed 38604812
CD37 is a safe chimeric antigen receptor target to treat acute myeloid leukemia
Cell Rep Med, 5 (6), 101572
DOI 10.1016/j.xcrm.2024.101572, PubMed 38754420
Transient TCR-based T cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer
Mol Ther, 32 (6), 2021-2029
DOI 10.1016/j.ymthe.2024.04.009, PubMed 38582964
Protocol for the development of a bioluminescent AML-PDX mouse model for the evaluation of CAR T cell therapy
STAR Protoc, 5 (4), 103522
DOI 10.1016/j.xpro.2024.103522, PubMed 39673705
Publications 2023
Efficient chimeric antigen receptor targeting of a central epitope of CD22
J Biol Chem, 299 (7), 104883
DOI 10.1016/j.jbc.2023.104883, PubMed 37269947
Determination of CAR T cell metabolism in an optimized protocol
Front Bioeng Biotechnol, 11, 1207576
DOI 10.3389/fbioe.2023.1207576, PubMed 37409169
In vitro re-challenge of CAR T cells
Methods Cell Biol, 183, 335-353
DOI 10.1016/bs.mcb.2023.06.003, PubMed 38548418
ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma
Nat Commun, 14 (1), 3375
DOI 10.1038/s41467-023-39097-x, PubMed 37291203
Publications 2022
CAR-Ts: new perspectives in cancer therapy
FEBS Lett, 596 (4), 403-416
DOI 10.1002/1873-3468.14270, PubMed 34978080
PD-L1 CAR effector cells induce self-amplifying cytotoxic effects against target cells
J Immunother Cancer, 10 (1)
DOI 10.1136/jitc-2021-002500, PubMed 35078921
How CAR T Cells Breathe
Cells, 11 (9)
DOI 10.3390/cells11091454, PubMed 35563759
Mechanism of CD79A and CD79B Support for IgM+ B Cell Fitness through B Cell Receptor Surface Expression
J Immunol, 209 (10), 2042-2053
DOI 10.4049/jimmunol.2200144, PubMed 36426942
A phase I/II escalation trial design T-RAD: Treatment of metastatic lung cancer with mRNA-engineered T cells expressing a T cell receptor targeting human telomerase reverse transcriptase (hTERT)
Front Oncol, 12, 1031232
DOI 10.3389/fonc.2022.1031232, PubMed 36439452
Publications 2021
Pharmacologic Control of CAR T Cells
Int J Mol Sci, 22 (9)
DOI 10.3390/ijms22094320, PubMed 33919245
Targeting KRAS mutations with HLA class II-restricted TCRs for the treatment of solid tumors
Oncoimmunology, 10 (1), 1936757
DOI 10.1080/2162402X.2021.1936757, PubMed 34235003
In vivo experimental mouse model to test CD19CAR T cells generated with different methods
Methods Cell Biol, 167, 149-161
DOI 10.1016/bs.mcb.2021.11.001, PubMed 35152992
Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
Int J Mol Sci, 22 (7)
DOI 10.3390/ijms22073561, PubMed 33808082
"Built-in" PD-1 blocker to rescue NK-92 activity from PD-L1-mediated tumor escape mechanisms
FASEB J, 35 (9), e21750
DOI 10.1096/fj.202100025R, PubMed 34424568
Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton
J Cell Sci, 134 (18)
DOI 10.1242/jcs.259221, PubMed 34494097
Publications 2020
Gene Editing in B-Lymphoma Cell Lines Using CRISPR/Cas9 Technology
Methods Mol Biol, 2115, 445-454
DOI 10.1007/978-1-0716-0290-4_25, PubMed 32006416
SJI 2020 special issue: A catalogue of Ovarian Cancer targets for CAR therapy
Scand J Immunol, 92 (4), e12917
DOI 10.1111/sji.12917, PubMed 32557659
Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy
Mol Ther, 29 (3), 1199-1213
DOI 10.1016/j.ymthe.2020.11.019, PubMed 33212301
Colorectal cysts as a validating tool for CAR therapy
BMC Biotechnol, 20 (1), 30
DOI 10.1186/s12896-020-00623-0, PubMed 32487146
Long-term surviving cancer patients as a source of therapeutic TCR
Cancer Immunol Immunother, 69 (5), 859-865
DOI 10.1007/s00262-019-02468-9, PubMed 31915853
Sympathetic improvement of cancer vaccine efficacy
Hum Vaccin Immunother, 16 (8), 1888-1890
DOI 10.1080/21645515.2019.1703456, PubMed 31977269
Combinatorial CAR design improves target restriction
J Biol Chem, 296, 100116
DOI 10.1074/jbc.RA120.016234, PubMed 33234592
Correction to: Preclinical assessment of transiently TCR redirected T cells for solid tumour immunotherapy
Cancer Immunol Immunother, 69 (1), 159-161
DOI 10.1007/s00262-019-02409-6, PubMed 31776597
T cell receptor therapy against melanoma-Immunotherapy for the future?
Scand J Immunol, 92 (4), e12927
DOI 10.1111/sji.12927, PubMed 32640053
Next Generation of Adoptive T Cell Therapy Using CRISPR/Cas9 Technology: Universal or Boosted?
Methods Mol Biol, 2115, 407-417
DOI 10.1007/978-1-0716-0290-4_22, PubMed 32006413
Publications 2019
TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma
Cancer Immunol Res, 7 (3), 355-362
DOI 10.1158/2326-6066.CIR-18-0351, PubMed 30659053
Chimeric antigen receptor preparation from hybridoma to T-cell expression
Antib Ther, 2 (2), 56-63
DOI 10.1093/abt/tbz007, PubMed 33928223
Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma
Blood Adv, 3 (8), 1230-1243
DOI 10.1182/bloodadvances.2018029678, PubMed 30979721
Treating osteosarcoma with CAR T cells
Scand J Immunol, 89 (3), e12741
DOI 10.1111/sji.12741, PubMed 30549299
NK cells specifically TCR-dressed to kill cancer cells
EBioMedicine, 40, 106-117
DOI 10.1016/j.ebiom.2019.01.031, PubMed 30665853
Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity
Oncoimmunology, 8 (3), 1558663
DOI 10.1080/2162402X.2018.1558663, PubMed 30723591
Preclinical assessment of transiently TCR redirected T cells for solid tumour immunotherapy
Cancer Immunol Immunother, 68 (8), 1235-1243
DOI 10.1007/s00262-019-02356-2, PubMed 31214732
Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT-tamoxifen hybrid therapy
NPJ Breast Cancer, 5, 13
DOI 10.1038/s41523-019-0108-8, PubMed 30993194
Publications 2018
A Spheroid Killing Assay by CAR T Cells
J Vis Exp (142)
DOI 10.3791/58785, PubMed 30596389
Breadth and Dynamics of HLA-A2- and HLA-B7-Restricted CD8+ T Cell Responses against Nonstructural Viral Proteins in Acute Human Tick-Borne Encephalitis Virus Infection
Immunohorizons, 2 (6), 172-184
DOI 10.4049/immunohorizons.1800029, PubMed 31022685
Artesunate shows potent anti-tumor activity in B-cell lymphoma
J Hematol Oncol, 11 (1), 23
DOI 10.1186/s13045-018-0561-0, PubMed 29458389
Publications 2017
BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF-β receptor type I ALK5
PLoS One, 12 (5), e0177188
DOI 10.1371/journal.pone.0177188, PubMed 28489883
Human c-SRC kinase (CSK) overexpression makes T cells dummy
Cancer Immunol Immunother, 67 (4), 525-536
DOI 10.1007/s00262-017-2105-9, PubMed 29248956
T cell therapy targeting a public neoantigen in microsatellite instable colon cancer reduces in vivo tumor growth
Oncoimmunology, 6 (4), e1302631
DOI 10.1080/2162402X.2017.1302631, PubMed 28507809
Fishing therapeutic T-cell receptors in healthy donor blood, is safety predictable?
Transl. Cancer Res., 6 3, S622-S624
DOI 10.21037/tcr.2017.05.25
A TCR-based Chimeric Antigen Receptor
Sci Rep, 7 (1), 10713
DOI 10.1038/s41598-017-11126-y, PubMed 28878363
Publications 2016
Enhancing Antitumor Immune Responses by Optimized Combinations of Cell-penetrating Peptide-based Vaccines and Adjuvants
Mol Ther, 24 (9), 1675-85
DOI 10.1038/mt.2016.134, PubMed 27377043
T-helper cell receptors from long-term survivors after telomerase cancer vaccination for use in adoptive cell therapy
Oncoimmunology, 5 (12), e1249090
DOI 10.1080/2162402X.2016.1249090, PubMed 28123886
Targeting B-cell neoplasia with T-cell receptors recognizing a CD20-derived peptide on patient-specific HLA
Oncoimmunology, 5 (5), e1138199
DOI 10.1080/2162402X.2016.1138199, PubMed 27467957
Distinct patterns of B-cell receptor signaling in non-Hodgkin lymphomas identified by single-cell profiling
Blood, 129 (6), 759-770
DOI 10.1182/blood-2016-05-718494, PubMed 28011673
Publications 2015
Unpredicted phenotypes of two mutants of the TcR DMF5
J Immunol Methods, 425, 37-44
DOI 10.1016/j.jim.2015.06.006, PubMed 26079729
Deciphering the Nongenomic, Mitochondrial Toxicity of Tamoxifens As Determined by Cell Metabolism and Redox Activity
ACS Chem Biol, 11 (1), 251-62
DOI 10.1021/acschembio.5b00734, PubMed 26569462
Soluble T-cell receptors produced in human cells for targeted delivery
PLoS One, 10 (4), e0119559
DOI 10.1371/journal.pone.0119559, PubMed 25875651
Publications 2013
BiP negatively affects ricin transport
Toxins (Basel), 5 (5), 969-82
DOI 10.3390/toxins5050969, PubMed 23666197
Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes
Proc Natl Acad Sci U S A, 111 (1), 403-8
DOI 10.1073/pnas.1306549111, PubMed 24344295
Invariant chain as a vehicle to load antigenic peptides on human MHC class I for cytotoxic T-cell activation
Eur J Immunol, 44 (3), 774-84
DOI 10.1002/eji.201343671, PubMed 24293164
Publications 2012
Role of Smad proteins in resistance to BMP-induced growth inhibition in B-cell lymphoma
PLoS One, 7 (10), e46117
DOI 10.1371/journal.pone.0046117, PubMed 23049692
Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the importins Kpnα1 and Kpnβ1
Traffic, 13 (5), 650-64
DOI 10.1111/j.1600-0854.2012.01341.x, PubMed 22321063
Publications 2011
T cells raised against allogeneic HLA-A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells
Int J Cancer, 130 (8), 1821-32
DOI 10.1002/ijc.26209, PubMed 21630262
A single point mutation in ricin A-chain increases toxin degradation and inhibits EDEM1-dependent ER retrotranslocation
Biochem J, 436 (2), 371-85
DOI 10.1042/BJ20101493, PubMed 21388347
A practical approach to T-cell receptor cloning and expression
PLoS One, 6 (11), e27930
DOI 10.1371/journal.pone.0027930, PubMed 22132171
Publications 2010
Targeting B cell leukemia with highly specific allogeneic T cells with a public recognition motif
Leukemia, 24 (11), 1901-9
DOI 10.1038/leu.2010.186, PubMed 20844564
Transiently redirected T cells for adoptive transfer
Cytotherapy, 13 (5), 629-40
DOI 10.3109/14653249.2010.542461, PubMed 21174490
Splice variants of enigma homolog, differentially expressed during heart development, promote or prevent hypertrophy
Cardiovasc Res, 86 (3), 374-82
DOI 10.1093/cvr/cvq023, PubMed 20097676
Publications 2009
Glycosphingolipid requirements for endosome-to-Golgi transport of Shiga toxin
Traffic, 10 (7), 868-82
DOI 10.1111/j.1600-0854.2009.00919.x, PubMed 19453975
SNX4 in complex with clathrin and dynein: implications for endosome movement
PLoS One, 4 (6), e5935
DOI 10.1371/journal.pone.0005935, PubMed 19529763
β-arrestins attenuate p38-mediated endosome to Golgi transport
Cell Microbiol, 11 (5), 796-807
DOI 10.1111/j.1462-5822.2009.01292.x, PubMed 19159388
Dendritic cells engineered to express defined allo-HLA peptide complexes induce antigen-specific cytotoxic T cells efficiently killing tumour cells
Scand J Immunol, 69 (4), 319-28
DOI 10.1111/j.1365-3083.2008.02223.x, PubMed 19284496
Characterization of clathrin and Syk interaction upon Shiga toxin binding
Cell Signal, 21 (7), 1161-8
DOI 10.1016/j.cellsig.2009.03.005, PubMed 19289168
Publications 2008
Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel
Cardiovasc Res, 78 (3), 458-65
DOI 10.1093/cvr/cvn052, PubMed 18296710
beta-catenin is involved in N-cadherin-dependent adhesion, but not in canonical Wnt signaling in E2A-PBX1-positive B acute lymphoblastic leukemia cells
Exp Hematol, 37 (2), 225-33
DOI 10.1016/j.exphem.2008.10.007, PubMed 19101069
Phosphorylation of fibroblast growth factor (FGF) receptor 1 at Ser777 by p38 mitogen-activated protein kinase regulates translocation of exogenous FGF1 to the cytosol and nucleus
Mol Cell Biol, 28 (12), 4129-41
DOI 10.1128/MCB.02117-07, PubMed 18411303
Vector-based delivery of siRNAs: in vitro and in vivo challenges
Front Biosci, 13, 3488-93
DOI 10.2741/2943, PubMed 18508450
Publications 2007
Axonal guidance protein FEZ1 associates with tubulin and kinesin motor protein to transport mitochondria in neurites of NGF-stimulated PC12 cells
Biochem Biophys Res Commun, 361 (3), 605-10
DOI 10.1016/j.bbrc.2007.07.050, PubMed 17669366
Phosphoinositide-regulated retrograde transport of ricin: crosstalk between hVps34 and sorting nexins
Traffic, 8 (3), 297-309
DOI 10.1111/j.1600-0854.2006.00527.x, PubMed 17319803
Protein kinase Cdelta is activated by Shiga toxin and regulates its transport
J Biol Chem, 282 (22), 16317-28
DOI 10.1074/jbc.M610886200, PubMed 17403690
The Mitogen-activated protein kinase p38 links Shiga Toxin-dependent signaling and trafficking
Mol Biol Cell, 19 (1), 95-104
DOI 10.1091/mbc.e07-06-0565, PubMed 17959827
Publications 2006
The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor
Mol Biol Cell, 17 (6), 2513-23
DOI 10.1091/mbc.e05-10-0915, PubMed 16554368
Transcriptional targeting of small interfering RNAs into cancer cells
Biochem Biophys Res Commun, 350 (4), 854-9
DOI 10.1016/j.bbrc.2006.09.127, PubMed 17034763
EDEM is involved in retrotranslocation of ricin from the endoplasmic reticulum to the cytosol
Mol Biol Cell, 17 (4), 1664-75
DOI 10.1091/mbc.e05-10-0961, PubMed 16452630
Transport of ricin from endosomes to the Golgi apparatus is regulated by Rab6A and Rab6A'
Traffic, 7 (6), 663-72
DOI 10.1111/j.1600-0854.2006.00418.x, PubMed 16683916
Publications 2005
Golgi vesiculation induced by cholesterol occurs by a dynamin- and cPLA2-dependent mechanism
Traffic, 6 (2), 144-56
DOI 10.1111/j.1600-0854.2005.00258.x, PubMed 15634214
The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity
J Neurosci, 25 (11), 2793-802
DOI 10.1523/JNEUROSCI.4090-04.2005, PubMed 15772339
Shiga toxin regulates its entry in a Syk-dependent manner
Mol Biol Cell, 17 (3), 1096-109
DOI 10.1091/mbc.e05-08-0766, PubMed 16371508
Strategies for the design of random siRNA libraries and the selection of anti-GFP siRNAs
Methods Mol Biol, 309, 83-91
DOI 10.1385/1-59259-935-4:083, PubMed 15990399
Reconstitution of active diphtheria toxin based on a hexahistidine tagged version of the B-fragment produced to high yields in bacteria
Toxicon, 46 (8), 900-6
DOI 10.1016/j.toxicon.2005.08.015, PubMed 16260019
Sap-1/PTPRH activity is regulated by reversible dimerization
Biochem Biophys Res Commun, 331 (2), 497-502
DOI 10.1016/j.bbrc.2005.03.196, PubMed 15850787
Publications 2003
Mapping of synergistic components of weakly interacting protein-protein motifs using arrays of paired peptides
J Biol Chem, 278 (17), 15162-7
DOI 10.1074/jbc.M211887200, PubMed 12551909
Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor
Mol Endocrinol, 17 (11), 2228-39
DOI 10.1210/me.2003-0011, PubMed 12907755
PTPH1 is a predominant protein-tyrosine phosphatase capable of interacting with and dephosphorylating the T cell receptor zeta subunit
J Biol Chem, 279 (9), 7760-9
DOI 10.1074/jbc.M309994200, PubMed 14672952
Probing protein-tyrosine phosphatase substrate specificity using a phosphotyrosine-containing phage library
J Biol Chem, 279 (1), 311-8
DOI 10.1074/jbc.M307617200, PubMed 14578355
Publications 2002
Protein tyrosine phosphatases as drug targets: PTP1B and beyond
Expert Opin Ther Targets, 6 (6), 637-47
DOI 10.1517/14728222.6.6.637, PubMed 12472377
Publications 2001
Pulling strings below the surface: hormone receptor signaling through inhibition of protein tyrosine phosphatases
Endocrine, 15 (1), 19-28
DOI 10.1385/endo:15:1:019, PubMed 11572321
Publications 2000
MetaBlasts: tracing protein tyrosine phosphatase gene family roots from Man to Drosophila melanogaster and Caenorhabditis elegans genomes
Gene, 253 (2), 137-43
DOI 10.1016/s0378-1119(00)00275-4, PubMed 10940550
Identification of tyrosine phosphatases that dephosphorylate the insulin receptor. A brute force approach based on "substrate-trapping" mutants
J Biol Chem, 275 (13), 9792-6
DOI 10.1074/jbc.275.13.9792, PubMed 10734133