EPFL BioE Talks SERIES "The Glycosphingolipid Gb3 as Target for Pathogens and Cancer Immunotherapy"
Event details
| Date | 15.04.2024 |
| Hour | 12:15 › 13:15 |
| Speaker | Prof. Winfried Römer, Faculty of Biology and Signalling Research Centres BIOSS and CIBSS, University of Freiburg (DE) |
| Location | Online |
| Category | Conferences - Seminars |
| Event Language | English |
WEEKLY EPFL BIOE TALKS SERIES (sandwiches provided)
Abstract:
Glycosphingolipids (GSLs) are mainly present in the extracellular leaflet of the plasma membrane. They are known to be involved in many cellular processes, e.g. in signal transduction, cell differentiation, apoptosis or embryonic development. However, a more precise characterization of the physiological role of GSLs is difficult due to the lack of appropriate tools.
This presentation focuses on the glycosphingolipid Gb3, also known as globotriaosylceramide, CD77 and Pk blood group antigen. It represents an attractive host cell receptor, particularly for pathogens and pathogenic products. Shiga toxin (Stx), from Shigella dysenteriae or Escherichia coli, which is one of the most virulent bacterial toxins, binds and clusters Gb3, leading to local negative membrane curvature and the formation of tubular plasma membrane invaginations as the initial step for clathrin-independent endocytosis. After internalization, Stx is embracing the retrograde transport pathway. In comparison, the homotetrameric lectin LecA from the bacterium Pseudomonas aeruginosa can also bind to Gb3, triggering the so-called lipid zipper mechanism, which results in membrane engulfment of the bacterium as an important step for its cellular uptake. Notably, both lectins bind to Gb3 but induce distinct plasma membrane domains and exploit mainly different transport pathways. What makes the difference?
The second part of the presentation will focus on the glycosphingolipid Gb3 as target for cancer immunotherapy. Gb3 is highly abundant in various cancers, such as Burkitt's lymphoma, colorectal or breast cancer. Proof-of-concept studies of lectin-based approaches (so-called lectibodies and lectin-CAR T cells), which redirect the immune system into fighting cancer, will be introduced.
The lectibody is a bispecific construct composed of a Gb3-binding lectin linked to an antibody fragment. It was inspired by bispecific T cell engager (BiTEs) antibodies that recruit cytotoxic T lymphocytes while simultaneously binding to tumor-associated antigens on cancer cells. In another approach, a panel of Gb3-binding lectin-CAR T cells was developed. Both tools resulted in a specific and nearly complete tumor cell lysis in vitro. These findings reveal the big potential of lectibodies and lectin-based CAR T cells as therapeutical applications to target Gb3 and other tumor-associated carbohydrate antigens expressed in hematological malignancies and solid tumors.
Bio:
Winfried Römer is Professor of Synthetic Biology of Signalling Processes at the Faculty of Biology and member of the BIOSS and CIBSS signaling research centers at the University of Freiburg (Germany) since 2011. From 1996-2001, he studied chemistry and biology at the University of Regensburg (Germany), where he also performed his PhD studies (2001-2004). As post-doctoral fellow (2004-2008) and research scientist CNRS (2008-2011) at Curie Institute (Paris, France), he investigated novel uptake pathways used by several toxins and viruses. Together with a colleague, he was awarded the Pfizer Foundation Research Prize (Infectiology) in 2011.
His research is mainly focused on host-pathogen interactions; in particular, he is interested in understanding the impact of bacterial lectins on host cell physiology of single cells, tissues and model organisms in molecular detail by using a combination of analytical and synthetic approaches. For instance, his lab investigates the effects of the P. aeruginosa lectins LecA and LecB on wound healing processes (e.g. cell proliferation, cell adhesion and migration, immune response). Moreover, in collaboration with chemists he develops alternative strategies to fight bacterial infections, e.g. divalent glycomimetics that fully block host cell invasion when applied in nano-molar concentrations, or bacteriophages to kill intracellular bacteria. Recently, he started to develop lectin-based tools to target and kill cancer cells.
Zoom link (with one-time registration for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks
Instructions for 1st-year Ph.D. students who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
Abstract:
Glycosphingolipids (GSLs) are mainly present in the extracellular leaflet of the plasma membrane. They are known to be involved in many cellular processes, e.g. in signal transduction, cell differentiation, apoptosis or embryonic development. However, a more precise characterization of the physiological role of GSLs is difficult due to the lack of appropriate tools.
This presentation focuses on the glycosphingolipid Gb3, also known as globotriaosylceramide, CD77 and Pk blood group antigen. It represents an attractive host cell receptor, particularly for pathogens and pathogenic products. Shiga toxin (Stx), from Shigella dysenteriae or Escherichia coli, which is one of the most virulent bacterial toxins, binds and clusters Gb3, leading to local negative membrane curvature and the formation of tubular plasma membrane invaginations as the initial step for clathrin-independent endocytosis. After internalization, Stx is embracing the retrograde transport pathway. In comparison, the homotetrameric lectin LecA from the bacterium Pseudomonas aeruginosa can also bind to Gb3, triggering the so-called lipid zipper mechanism, which results in membrane engulfment of the bacterium as an important step for its cellular uptake. Notably, both lectins bind to Gb3 but induce distinct plasma membrane domains and exploit mainly different transport pathways. What makes the difference?
The second part of the presentation will focus on the glycosphingolipid Gb3 as target for cancer immunotherapy. Gb3 is highly abundant in various cancers, such as Burkitt's lymphoma, colorectal or breast cancer. Proof-of-concept studies of lectin-based approaches (so-called lectibodies and lectin-CAR T cells), which redirect the immune system into fighting cancer, will be introduced.
The lectibody is a bispecific construct composed of a Gb3-binding lectin linked to an antibody fragment. It was inspired by bispecific T cell engager (BiTEs) antibodies that recruit cytotoxic T lymphocytes while simultaneously binding to tumor-associated antigens on cancer cells. In another approach, a panel of Gb3-binding lectin-CAR T cells was developed. Both tools resulted in a specific and nearly complete tumor cell lysis in vitro. These findings reveal the big potential of lectibodies and lectin-based CAR T cells as therapeutical applications to target Gb3 and other tumor-associated carbohydrate antigens expressed in hematological malignancies and solid tumors.
Bio:
Winfried Römer is Professor of Synthetic Biology of Signalling Processes at the Faculty of Biology and member of the BIOSS and CIBSS signaling research centers at the University of Freiburg (Germany) since 2011. From 1996-2001, he studied chemistry and biology at the University of Regensburg (Germany), where he also performed his PhD studies (2001-2004). As post-doctoral fellow (2004-2008) and research scientist CNRS (2008-2011) at Curie Institute (Paris, France), he investigated novel uptake pathways used by several toxins and viruses. Together with a colleague, he was awarded the Pfizer Foundation Research Prize (Infectiology) in 2011.
His research is mainly focused on host-pathogen interactions; in particular, he is interested in understanding the impact of bacterial lectins on host cell physiology of single cells, tissues and model organisms in molecular detail by using a combination of analytical and synthetic approaches. For instance, his lab investigates the effects of the P. aeruginosa lectins LecA and LecB on wound healing processes (e.g. cell proliferation, cell adhesion and migration, immune response). Moreover, in collaboration with chemists he develops alternative strategies to fight bacterial infections, e.g. divalent glycomimetics that fully block host cell invasion when applied in nano-molar concentrations, or bacteriophages to kill intracellular bacteria. Recently, he started to develop lectin-based tools to target and kill cancer cells.
Zoom link (with one-time registration for the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalks
Instructions for 1st-year Ph.D. students who are under EDBB’s mandatory seminar attendance rule:
IN CASE you cannot attend in-person in the room, please make sure to
- send D. Reinhard a note well ahead of time (ideally before seminar day), informing that you plan to attend the talk online, and, during seminar:
- be signed in on Zoom with a recognizable user name (not any alias making it difficult or impossible to identify you).
Practical information
- Informed public
- Registration required
Organizer
- Prof. Giovanni D'Angelo, EPFL
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD