Nicolas van Baren
Senior Investigator
Sophie Lucas
Immuniteit & Cancer
Institut de Duve Avenue Hippocrate 74 - B1.74.04 1200 Bruxelles
The Lucas Lab studies how Tregs and TGF-β suppress immune responses in patients with cancer or auto-immune diseases.
Major achievements
- Monoclonal antibodies to block TGF-β1 production and immunosuppression by GARP+ Tregs to treat patients with cancer (in clinical trials since 2019)
- ERC Consolidator Grant (2016-2021)
- Partnerships with industry (argenx since 2015; AbbVie since 2019)
Research
Question
What mechanisms enable immunosuppressive cells to produce TGF-β, and can we target them with new drugs to treat cancer or other immune-related diseases ?
Research focus
3D structure of TGF-β1 presented by GARP on Tregs, bound and blocked by an anti-GARP antibody which could serve currently tested in the clinics for the immunotherapy of cancer.
Our research focuses on understanding the molecular mechanisms by which cells known as Tregs suppress immune responses, with the long-term objective to develop new drugs to treat patients with cancer or auto-immune diseases. We found out previously that production of TGF-β1 is one important mechanism by which Tregs suppress anti-tumor immunity in cancer patients. TGF-β1, β2, and β3 molecules are closely related members of the Transforming Growth Factor beta (TGF-β) superfamily of growth factors. They are encoded by distinct genes and exert major roles during organ development in utero, and in wound healing and immune responses in adults. Owing to their potency and variety of effects, the three TGF-βs are produced as latent, inactive precursors that require activation to exert biological activity. The mechanisms of TGF-β activation appear to be isoform- and cell type-specific. We discovered a mechanism of TGF-β1 activation that operates on the surface of human Tregs and implies transmembrane proteins GARP and αVβ8. We developed antibodies binding GARP:TGF-β1 complexes that block TGF-β1 activation and immunosuppression by Tregs. One of our antibodies is currently tested in clinical trials for cancer immunotherapy.
At variance with our laboratory’s previous major interests in oncology, we are now also exploring the role of GARP-dependent and -independent activation of TGF-β isoforms in auto- and allo-immune responses, with the goal of developing new therapeutic approaches for patients suffering from auto-immunity or graft-versus-host disease.
Projects
- TGF-ß1, ß2 and ß3 production by immunosuppressive cells in auto- and allo-immune diseases
- Antibodies blocking TGF-ß1 production and immunosuppression by GARP-expressing Tregs for the immunotherapy of cancer
Ziekten
Team
Clinical Investigator
Postdoctoral Scientists
PhD Students
Master Student
Research Assistants
Administrative Support
Therapeutic activity of GARP:TGF-ß1 blockade in murine primary myelofibrosis.
Lecomte S, Devreux J, de Streel G, van Baren N, Havelange V, Schröder D, Vaherto N, Vanhaver C, Vanderaa C, Dupuis N, Pecquet C, Coulie PG, Constantinescu SN and Lucas S.
Blood (2023) 141(5):490-502.
Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer
de Streel G, Bertrand C, Chalon N, Liénart S, Bricard O, Lecomte S, Devreux J, Gaignage M, De Boeck G, Mariën L, Van De Walle I, van der Woning B, Saunders M, de Haard H, Vermeersch E, Maes W, Deckmyn H, Coulie PG, van Baren N, Lucas S.
Nat Comm (2020) 11(1):4545.
Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells.
Liénart S, Merceron R, Vanderaa C, Lambert F, Colau D, Stockis J, van der Woning B, De Haard H, Saunders M, Coulie PG, Savvides SN, Lucas S.
Science (2018) 362(6417):952-956.
Hippocrateslaan 75 - 1200 Brussel - BELGIE
BTW : BE0423 837 837
Tel : +32 2 434 75 50