A stable, engineered TL1A ligand co-stimulates T cells via specific binding to DR3.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 11 2022
29 11 2022
Historique:
received:
26
06
2022
accepted:
23
11
2022
entrez:
29
11
2022
pubmed:
30
11
2022
medline:
2
12
2022
Statut:
epublish
Résumé
TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflammatory cytokines. We designed a stable recombinant TL1A molecule that (1) displays high monodispersity and stability, (2) displays the ability to activate T cells in vitro and in vivo, and (3) lacks binding to DcR3 while retaining functional activity via DR3. Together these results suggest the TL1A ligand can be amenable to therapeutic development on its own or paired with a tumor-targeting moiety.
Identifiants
pubmed: 36446890
doi: 10.1038/s41598-022-24984-y
pii: 10.1038/s41598-022-24984-y
pmc: PMC9709071
doi:
Substances chimiques
Tumor Necrosis Factor Ligand Superfamily Member 15
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20538Informations de copyright
© 2022. The Author(s).
Références
Croft, M., Benedict, C. A. & Ware, C. F. Clinical targeting of the TNF and TNFR superfamilies. Nat. Rev. Drug Discov. 12, 147–168 (2013).
doi: 10.1038/nrd3930
pubmed: 23334208
pmcid: 3625401
Zou, W., Wolchok, J. D. & Chen, L. PD-L1 (B7–H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl. Med. 8, 328rv324 (2016).
doi: 10.1126/scitranslmed.aad7118
Wolchok, J. D. et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 377, 1345–1356 (2017).
doi: 10.1056/NEJMoa1709684
pubmed: 28889792
pmcid: 5706778
Chen, L. & Flies, D. B. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 13, 227–242 (2013).
doi: 10.1038/nri3405
pubmed: 23470321
pmcid: 3786574
Saito, T. Molecular dynamics of co-signal molecules in T-cell activation. Adv. Exp. Med. Biol. 1189, 135–152 (2019).
doi: 10.1007/978-981-32-9717-3_5
pubmed: 31758533
Richard, A. C. et al. The TNF-family cytokine TL1A: From lymphocyte costimulator to disease co-conspirator. J. Leukoc. Biol. 98, 333–345 (2015).
doi: 10.1189/jlb.3RI0315-095R
pubmed: 26188076
pmcid: 4763597
Hsieh, S. L. & Lin, W. W. Decoy receptor 3: An endogenous immunomodulator in cancer growth and inflammatory reactions. J. Biomed. Sci. 24, 39 (2017).
doi: 10.1186/s12929-017-0347-7
pubmed: 28629361
pmcid: 5477258
Lin, W. W. & Hsieh, S. L. Decoy receptor 3: A pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer. Biochem. Pharmacol. 81, 838–847 (2011).
doi: 10.1016/j.bcp.2011.01.011
pubmed: 21295012
Wei, Y. et al. DcR3 promotes proliferation and invasion of pancreatic cancer via a DcR3/STAT1/IRF1 feedback loop. Am. J. Cancer Res. 9, 2618–2633 (2019).
pubmed: 31911850
pmcid: 6943350
Zhang, H. et al. DcR3 promotes hepatoma cell migration by downregulating E-cadherin expression. Oncol Rep 38, 377–383 (2017).
doi: 10.3892/or.2017.5685
pubmed: 28560426
Liu, W. et al. Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: Structure of the LIGHT:DcR3 assembly. Structure 22, 1252–1262 (2014).
doi: 10.1016/j.str.2014.06.013
pubmed: 25087510
pmcid: 4163024
Banfield, C. et al. First-in-human, randomized dose-escalation study of the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of PF-06480605 in healthy subjects. Br. J. Clin. Pharmacol. 86, 812–824 (2020).
doi: 10.1111/bcp.14187
pubmed: 31758576
pmcid: 7098865
Zhan, C. et al. Biochemical and structural characterization of the human TL1A ectodomain. Biochemistry 48, 7636–7645 (2009).
doi: 10.1021/bi900031w
pubmed: 19522538
Zhan, C. et al. Decoy strategies: The structure of TL1A:DcR3 complex. Structure 19, 162–171 (2011).
doi: 10.1016/j.str.2010.12.004
pubmed: 21300286
pmcid: 3065972
Strohl, W. R. Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs 29, 215–239 (2015).
doi: 10.1007/s40259-015-0133-6
pubmed: 26177629
pmcid: 4562006
Bossen, C. et al. Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human. J Biol Chem 281, 13964–13971 (2006).
doi: 10.1074/jbc.M601553200
pubmed: 16547002
Anderson, K. G., Stromnes, I. M. & Greenberg, P. D. Obstacles posed by the tumor microenvironment to T cell activity: A case for synergistic therapies. Cancer Cell 31, 311–325 (2017).
doi: 10.1016/j.ccell.2017.02.008
pubmed: 28292435
pmcid: 5423788
Wang, L., Hoseini, S. S., Xu, H., Ponomarev, V. & Cheung, N. K. Silencing Fc domains in T cell-engaging bispecific antibodies improves T-cell trafficking and antitumor potency. Cancer Immunol. Res. 7, 2013–2024 (2019).
doi: 10.1158/2326-6066.CIR-19-0121
pubmed: 31615814
pmcid: 7398503
Wu, Z. & Cheung, N. V. T cell engaging bispecific antibody (T-BsAb): From technology to therapeutics. Pharmacol. Ther. 182, 161–175 (2018).
doi: 10.1016/j.pharmthera.2017.08.005
pubmed: 28834699
Tang, H. et al. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell 29, 285–296 (2016).
doi: 10.1016/j.ccell.2016.02.004
pubmed: 26977880
pmcid: 4794755
Tang, Z. et al. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45, W98–W102 (2017).
doi: 10.1093/nar/gkx247
pubmed: 28407145
pmcid: 5570223
Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997).
doi: 10.1016/S0076-6879(97)76066-X
pubmed: 27754618
Franke, D. & Svergun, D. I. DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering. J. Appl. Crystallogr. 42, 342–346 (2009).
doi: 10.1107/S0021889809000338
pubmed: 27630371
pmcid: 5023043
Blanchet, C. E. & Svergun, D. I. Small-angle X-ray scattering on biological macromolecules and nanocomposites in solution. Annu. Rev. Phys. Chem. 64, 37–54 (2013).
doi: 10.1146/annurev-physchem-040412-110132
pubmed: 23216378
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
doi: 10.1002/jcc.20084
pubmed: 15264254