Researchers from LIH have developed innovative artificial antibodies for cancer immunotherapy. The molecules bind selectively to cancer cells and lead to their destruction by the activation of the complement system. Significant funding has been allocated by the Luxembourg National Research Fund (FNR) to conduct preclinical studies and take this drug development project “from bench to bedside”.
Marking cancer cells to kill them
With conventional antibody-based immunotherapies, antibody binding is often below the threshold needed to trigger the assembly of the complement, a complex system of serum proteins that causes cell killing. Dr Xavier Dervillez and Dr Carole Devaux, researchers at LIH’s Department of Infection and Immunity, have developed artificial antibodies, called "CoMiX" for “complement multimeric immunotherapeutic complexes”, which can overcome this limitation. CoMiX strongly bind to the surface of cancer cells, contain multiple dimers of Fc fragments (antibody tail region) that ease the activation of the classical complement pathway (killing the cells by forming pores in their membrane), and can in addition simultaneously activate the alternative complement pathway (initiating the attack of cytotoxic immune cells).
‘CoMiX are modular, multivalent and multifunctional, and can hit cancer cells in different ways,’ says Dr Xavier Dervillez, inventor of the technology. ‘Our molecules are composed of a scaffold on which we can bind several entities. The most efficient molecule variants have a targeting function for the recognition of cancer cells and two effector functions that trigger the two pathways of the complement system.’
A long development process
The molecules have evolved since the beginning of the research project. The first generation was bifunctional, the second is trifunctional, allowing the simultaneous activation of several immune responses, which conventional antibodies are unable to achieve in anti-cancer therapy. A patent was filed in 2016 to protect the invention.
The molecules were successfully tested in cell culture for two types of cancer: breast cancer, representative of a "solid" cancer, and lymphoma, representative of a "liquid" cancer, indicating that the therapeutic strategy could be applied to several types of cancers. After more than four years of developing multiple types of CoMiX and verifying their efficiency in cell culture, the technology is now mature enough to move to the next stage of the drug development process: the preclinical phase.
The FNR financially supports the project with 500,000 Euros via its Proof-of-Concept (PoC) programme. This funding instrument aims to enable research institutes to validate and commercialise their scientific results. This is the first time that LIH is granted such a funding type. The researchers will now be able to conduct preclinical studies to confirm the effectiveness and safety of the molecules in vivo in mouse models.
The project is conducted in collaboration with Prof Iris Behrmann from the Life Sciences Research Unit of the University of Luxembourg and Prof Jacques Cohen from the Nanosciences Research Laboratory of the University of Reims Champagne-Ardenne. It has already attracted the attention of the pharmaceutical industry. ‘Some pharmaceutical companies have expressed their interest in our molecules," says Dr Carole Devaux, project manager. ‘We hope that following the results of the preclinical studies, they will formally engage in the project to drive it towards clinical application.’