A team led by Professor Tian Daishi from Tongji Hospital, Tongji Medical College at Huazhong University of Science and Technology (HUST), published the results of its Phase I clinical trial in The New England Journal of Medicine (NEJM) on Sept 3.

The study demonstrates the feasibility of using a lentiviral vector to induce in vivo production of CD19 CAR T-cells to treat autoimmune diseases of the nervous system, thereby eliminating the need for ex vivo cell modification and lymphodepleting chemotherapy.

Traditional CAR T therapy requires harvesting a patient's T cells, modifying and expanding them ex vivo, and then reinfusing them – a process that is time-consuming and costly. This study instead uses a self-inactivating, non-replicating lentiviral vector to deliver the CD19 CAR gene directly to the patient's T cells in vivo, enabling them to transform into CAR T-cells.

The study evaluated 16 patients diagnosed with four conditions: multiple sclerosis, MOG antibody-associated disease, myasthenia gravis, and idiopathic inflammatory myopathies.

Results showed that all participants generated and expanded CAR T-cells in vivo, resulting in effective depletion of B cells from peripheral blood, bone marrow, and cerebrospinal fluid. Approximately two months later, the reappearance of B cells was observed with a younger and more stable gene expression profile and B-cell receptor features, suggesting a potential immune system reset toward a new equilibrium.

After a median follow-up of six months, improvements were noted across clinical and laboratory indicators in all patient groups. However, as a small, single-arm Phase I trial without a control group, the therapeutic effects require further validation through larger clinical studies.

In terms of safety, 11 participants experienced mild Grade 1 cytokine release syndrome, which resolved within two weeks, and no severe treatment-related toxicities were reported. The study confirms the clinical feasibility of this approach, offering a simplified framework for CAR T-cell therapy that could improve accessibility.

Source: Tongji Hospital, Tongji Medical College, HUST