This trial is co-funded by the Enfants sans Cancer 2020 race and was selected following the Fight Kids Cancer call for projects that we launched in January 2020.
About CAR-T Cells
CAR-T cell therapy (Chimeric Antigen Receptor T-cell) is an emerging immunotherapy strategy for cancer treatment. These cells are genetically modified T lymphocytes designed to recognize and eliminate cancer cells. To carry out this cellular therapy, it is necessary to collect immune cells from a patient, purify the T lymphocytes, genetically modify them with a gene therapy vector, and reinject them.
T lymphocytes are responsible for the cellular immune response aimed at destroying various pathogens, including virus-infected cells and tumor cells. Typically, these cells are not sufficiently active because they are inhibited by cancer cells. The addition of a CAR receptor via gene therapy enhances their tumor recognition and makes them more active. The genetic modification also introduces a costimulatory element that activates the CAR-T cell and enables it to attack the cancer cell once it binds to it.
This treatment has already shown great efficacy for leukemia, but it appears more complex for solid tumors (a recent study has shown significant efficacy for neuroblastoma). One major problem is the difficulty of CAR-T cells reaching the tumor. The Imagine project aims to improve this by adding magnetic nanoparticles to the surface of these cells, thereby better guiding them to the tumor using a magnetic field.
About Imagine
The tumor microenvironment is very hostile to the infiltration, accumulation, and retention of lymphocytes. To address this, magnetic nanoparticles have been grafted onto CAR-T cells to facilitate their guidance to the tumor, in this case, osteosarcoma. The goal of this project is to demonstrate that this modification is feasible, non-toxic to T lymphocytes, does not alter their function, and indeed enhances their ability to target osteosarcoma cells.
Project Progress
Researchers involved in this project first tested several protocols for the design and grafting of nanoparticles. After identifying the method with the best yield, they demonstrated that it is possible to coat T lymphocytes with magnetic nanoparticles without affecting their viability or their ability to recognize and destroy a pathogen. These cells were then injected into mice, and a magnet was placed in a region containing lymph nodes. The researchers showed that neither the grafting of modified CAR-T cells nor the magnetic field disrupted the distribution of the animal’s native immune cells. However, a very high concentration of magnetic CAR-T lymphocytes was observed in the lymph nodes near the magnet. This indicates that these cells could pass from the blood to the lymph nodes easily due to the magnetic field. They are currently testing the efficacy of these cells in penetrating and potentially eradicating solid osteosarcoma tumors inoculated in mice. Furthermore, researchers are replicating this work on human CAR-T cells expressing CAR-NKG2D targeting osteosarcoma. Although the protocol had to be adjusted, functional magnetized human cells were obtained. Thanks to this work, which is nearing completion, it will likely be possible to clinically test these optimized immunotherapy cells in children with solid tumors such as osteosarcoma.
This work has been presented at numerous conferences and seminars (20), resulted in two publications currently under review, and a patent application.
Imagine Project Summary
- Coordinating Investigators: Drs. Antonio Perez Martinez, Domingo Barber, Sébastien Wälchli, Emmanuel Donnadieu
- Program Duration: January 2021 – January 2025
- Countries Involved: Spain, Norway, France, Greece
- Funding: Fight Kids Cancer: €500,000, including funding from Imagine for Margo: €239,448