Periodic Reporting for period 1 - THERA-LEGO (Commercial feasibility of a therapeutic approach to cancer based on ‘LEGO’ antibody recruiting glycodendrimers)
Periodo di rendicontazione: 2021-01-01 al 2022-06-30
Cancer remains a major cause of mortality worldwide, with projections estimating that 40% of population will be diagnosed
with a form of cancer during their lifetime. Despite significant progress in treatment modalities, current therapeutic regimens
are still deficient due to intolerable side effects, while stray cancer cells often escape destruction. Immunotherapy-based
approaches certainly represent the most promising alternatives in this area although very limited approaches are available.
In addition, major issues remain to be addressed such as the lack of efficiency and autoimmune toxicity for a large
population of patients. In the ERC Consolidator grant “LEGO”, we have demonstrated that fully synthetic structures with
unprecedented combinations have immunological properties against cancers. We have developed a “molecular LEGO”
approach to construct Antibody Recruiting Glycodendrimers (ARGs) embedded with key structural parameters and capable
of redirecting endogenous antibodies present in the human bloodstream against tumors without preliminary immunization.
Among a variety ARGs, we have identified two lead compound that: 1/ recruit natural Abs with a cluster of oligosaccharides;
2/ target cancer receptors with a cluster of peptides; 3/ promote the formation of a ternary complex between natural Abs and
cancer cells; 4/ promote up to 60% of cytotoxicity towards cancer cells in vitro. Within THERA-LEGO, we aim to investigate
the commercial feasibility and the in vivo properties of our lead compounds (toxicity, stability, biodistribution,
pharmacokinetics/dynamics, immunogenicity) in humanized mice models, to facilitate the transfer of the technology to a
company and the initiation of clinical development. The work to be done in this project will advance our assets from a
Technology Readiness Level (TRL) of 3 to 5 and will enable us to create an exploitation strategy (relying either on
commercialization through own spin-off or licensing to a pharma company).
with a form of cancer during their lifetime. Despite significant progress in treatment modalities, current therapeutic regimens
are still deficient due to intolerable side effects, while stray cancer cells often escape destruction. Immunotherapy-based
approaches certainly represent the most promising alternatives in this area although very limited approaches are available.
In addition, major issues remain to be addressed such as the lack of efficiency and autoimmune toxicity for a large
population of patients. In the ERC Consolidator grant “LEGO”, we have demonstrated that fully synthetic structures with
unprecedented combinations have immunological properties against cancers. We have developed a “molecular LEGO”
approach to construct Antibody Recruiting Glycodendrimers (ARGs) embedded with key structural parameters and capable
of redirecting endogenous antibodies present in the human bloodstream against tumors without preliminary immunization.
Among a variety ARGs, we have identified two lead compound that: 1/ recruit natural Abs with a cluster of oligosaccharides;
2/ target cancer receptors with a cluster of peptides; 3/ promote the formation of a ternary complex between natural Abs and
cancer cells; 4/ promote up to 60% of cytotoxicity towards cancer cells in vitro. Within THERA-LEGO, we aim to investigate
the commercial feasibility and the in vivo properties of our lead compounds (toxicity, stability, biodistribution,
pharmacokinetics/dynamics, immunogenicity) in humanized mice models, to facilitate the transfer of the technology to a
company and the initiation of clinical development. The work to be done in this project will advance our assets from a
Technology Readiness Level (TRL) of 3 to 5 and will enable us to create an exploitation strategy (relying either on
commercialization through own spin-off or licensing to a pharma company).