Sophie Lucas

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)

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

Sophie Lucas acquired an MD degree at the UCLouvain in 1994 and a PhD degree in 2000 for her work in tumor immunology under the mentorship of Thierry Boon. She identified genes encoding tumour-specific antigens, some of which were used in clinical trials of therapeutic vaccination against cancer. She studied new cytokines and their receptors during her post-doc at Genentech (San Francisco). In 2004, she founded her own group at the de Duve Institute, to identify molecular mechanisms by which cells known as Tregs suppress immune responses in cancer patients. The group developed an antibody to block TGF-β-mediated immunosuppression by Tregs, currently in clinical trials of cancer immunotherapy. They also studies immunosuppression by Tregs and TGF-β in other types of immune-related diseases.

Sophie Lucas was appointed F.R.S.-FNRS Research Associate in 2008, then Professor of Cancer Immunotherapy at the UCLouvain in 2016. She is an investigator of the WEL Research Institute since 2019. She became President of the de Duve Institute in 2019.

Honors

• Francqui Chair 2021-2022, UNamur
• Prix GSK-Vaccine 2016-2018
• Prix du Concours ordinaire de la deuxième Section de l’Académie Royale de Médecine de Belgique (2012)
• Team Science Recognition Award - International Society for Biological Therapy of Cancer - Society for Immunotherapy of Cancer (2010)

Affiliations

• Group Leader, de Duve Institute
• President of the de Duve Institute
• Professor of Cancer Immunotherapy, UCLouvain
• Investigator, WELBIO Department, WEL Research Institute