MONO-CHEM

The challenge. Harnessing monocytes, immune cells that naturally infiltrate solid tumors, as reprogrammable therapeutic vehicles to overcome cancers resistant to current immunotherapies.
Scientific stakes and expected impacts. CAR-T cell therapies have revolutionized the treatment of blood cancers but fail against solid tumors due to antigen escape, poor tumor infiltration, and local immunosuppression. MONO-CHEM proposes to overcome these limitations by engineering monocyte membranes through bioorthogonal chemistry. A universal receptor (CAR-K3) enables modular assembly of targeting adapters (E3@VHH) directed against different tumor antigens, making the system adaptable without cell re-manufacturing. The project also integrates local delivery of cytokines activated only within the acidic tumor microenvironment and real-time monitoring by PET imaging, paving the way for a truly theranostic and personalized cell therapy.
Societal stakes and expected impacts. Triple-negative breast cancer, the project’s target indication, represents a major unmet medical need with limited therapeutic options. By replacing complex biological components with standardized synthetic peptides and relying on production compatible with good manufacturing practices, MONO-CHEM aims to significantly reduce costs and production timelines compared to current autologous CAR-T therapies, thereby improving accessibility of innovative cellular immunotherapies for patients.
Main research axes. The project is organized around four complementary axes: (1) design and characterization of the E3@VHH adapter platform and conjugated therapeutic payloads (cytokines, antibodies); (2) genetic engineering of CAR-K3 monocytes and in vitro functional validation; (3) preclinical evaluation of antitumor efficacy, biodistribution, and safety in triple-negative breast cancer models; (4) transfer toward quasi-GMP production in partnership with the MTInov platform to prepare for clinical translation.

Monocytes are immune cells that circulate in the blood and can naturally travel into tumors.

The MONO-CHEM project aims to use these cells as “vehicles” that can deliver treatments directly to tumors. The researchers seek to modify monocytes to enhance their ability to recognize and attack cancer cells.

To achieve this, they will use methods that make it possible to precisely attach different molecules to the surface of monocytes. These molecules could include proteins that recognize tumor cells or molecules capable of stimulating the immune system. Once programmed, these monocytes could act as true “therapeutic Trojan horses”: they would travel to tumors and help eliminate cancer cells. They could also release molecules locally to stimulate the immune system and help the body mount a stronger response against the tumor.

One of the project’s goals is to develop this approach for difficult-to-treat cancers, such as triple-negative breast cancer, while promoting a lasting immune response that could help reduce the risk of relapse.

To carry out this project, MONO-CHEM brings together French partners with complementary expertise in cell engineering, gene therapy, immunotherapy, oncology, and the development of treatments for patients. By combining fundamental research, technological innovation, and clinical expertise, the consortium aims to turn this new approach into a future therapeutic strategy for difficult-to-treat solid tumors.