Lemtrada Targets Circulating Innate Immune Cells in RRMS Patients

Lemtrada (alemtuzumab), a humanized monoclonal antibody, is able to remodel the immune responses of innate immune cells in patients with relapsing-remitting multiple sclerosis (RRMS), according to a recent study. This previously unreported phenotype may contribute to the benefits of the drug for RRMS patients.

The study, “Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis,” was published in  Neurology: Neuroimmunology & Neuroinflammation.

Lemtrada targets a protein called CD52. The protein is present at the surface of certain white blood cells (key cells of the immune system called lymphocytes). After treatment with Lemtrada, the CD52-lymphocytes are targeted for destruction.

Lemtrada is an approved medicine for long-term suppression of disease activity in RRMS. Despite its effects on some cells in the immune system, including lymphocytes, how Lemtrada affects other types of immune cells in the innate immune system regarding RRMS is still questioned.

In the recent study, authors investigated the changes in innate immune cells, the first line of defense against pathogens present in blood circulation in RRMS patients, at different time-points: before taking Lemtrada and then six and 12 months after Lemtrada treatment. The team looked specifically at two types of cells, the myeloid (dendritic cells and macrophages) and innate lymphoid cells.

Researchers observed that when compared to a class of lymptocytes (the CD4 positive-T lymphocytes), the myeloid and lymphoid innate cells of patients with MS expressed significantly lower levels of CD52 at the cells’ surface.

Within six months of Lemtrada treatment, authors noted that the numbers of certain circulating innate immune cells (specifically dendritic cells) were reduced when compared to the start of the study. On the contrary, the number of another class of innate immune cells, a specific subset of natural killer cells that belong to the innate lymphoid cell lineage, increased under Lemtrada treatment — but their activity remained unchanged.

The results showed that six months of Lemtrada therapy lowers the number of dendritic cells while it induces an expansion of a subset of natural killer cells, supporting their activity as important immunoregulatory cells. This suggests that Lemtrada treatment in patients with RRMS can remodel components of the innate immune system, which may contribute to the drug’s long-term beneficial effects and preserve immune-competence in patients with RRMS.