MOHICAN

Research program

The objective is to dynamically characterize interactions between effector immune cells, target cells (notably tumor cells), and the immune
microenvironment. Although functional immunological assays are widely used in basic research, their complexity, slowness, and cost hinder their clinical integration. MOHICAN aims to overcome these limitations through a recently patented concept, leveraging the microtechnology expertise of partner laboratories at IINS and LAI. These multifunctional microsystems, based on subcellular-scale micropatterning, will enable fine-tuned modulation of the microenvironment, sorting, identification and positioning of cells, the delivery of spatially and temporally controlled activation signals, and the detection of cell surface markers and cytokine secretion.

Measurements will be conducted at the single-cell level, in real time, providing multiparametric kinetic data essential to understanding individual immune responses. The project will contribute to the development of innovative personalized immunotherapy strategies for hematologic cancers, in collaboration with clinicians from AP-HM (Assistance Publique–Hôpitaux de Marseille) and the Paoli-Calmettes Institute (regional cancer center). To this end, we will develop microdevices tailored to the specific functions of T lymphocytes, CAR-T cells, and NK cells. These systems will be tested in the context of monoclonal antibody therapies (for patient stratification and treatment decision support) and CAR-T cell therapies (for identifying predictive functional signatures during CAR-T cell preparation, testing cell products in production line before administration, and for post-treatment monitoring).

The clinical research protocols (CPP) required for these studies are already in place, along with biobanks containing patient samples accompanied by detailed clinical data and longitudinal follow-up. In parallel, the microchip fabrication process will be optimized and fully automated to ensure rigorous standardization and high-throughput production. A complete technological pipeline—from blood sampling to multiparametric readout of immune functions—will be implemented to enable the integration of this system into routine hospital workflows, addressing current limitations related to technical staff availability.

Expected Outcomes

The project is expected to deliver both scientific breakthroughs and medical advances, with a
significant impact in the field of immunotherapy monitoring and personalized medicine, in line with
the objectives of the PEPR MEDOOC program.

Medical Outcomes : routine hospital tools for

• Stratification of patients eligible for monoclonal antibody treatments.

• Selection of optimal therapeutic options based on a patient’s individual immune response.

• Pre-screening of patient-derived cells for personalized cell therapies such as CAR-T cells

• Monitoring of treatment efficacy and safety, including early detection of cytokine release
  syndromes, B-cell lymphopenia, or relapse. vThis tool could thus become a central companion
  diagnostic for immunotherapy in hospital settings.
• Standardize functional assays for with multicenter clinical trials and hospital environments.

Scientific Outcomes

• Provide a platform for studying functional heterogeneity at the single-cell level.
• Significantly advance automated and reproducible micropatterning workflows, both in open-well formats and within microfluidic channels, crucial for enabling functional assays from high-throughput screens to dynamic, perfused systems; set a new standard for pattern fidelity and assay reproducibility.

The consortium

The MOHICAN consortium brings together leading biophysics teams (LAI–Marseille and IINS–Bordeaux), clinical partners from AP-HM and IPC, and the genomics lab TAGC. These partners share a strong history of collaboration, joint publications, shared PhD supervision, and translational projects. Weekly and bi-monthly coordination meetings are already established. The technical development will be jointly conducted and transferred progressively to the hospital environment. Intellectual property will be co-managed by Inserm, CNRS, AMU, IPC, and AP-HM under a formal consortium agreement.