Ocrevus’s main immune cell target is B-cells, but a small study has shown that it can also lessen pro-inflammatory immune T-cells in patients with primary progressive multiple sclerosis.
Multiple Sclerosis (MS) is a chronic inflammatory, neurodegenerative, and demyelinating autoimmune disorder. The primary progressive form (PPMS) is characterized by a worsening of neurologic function with a gradual accumulation of disability from the onset of disease. The limited understanding of the pathogenesis of PPMS has hindered the development of reliable and effective treatments. However, there is an approved intravenous therapy, Ocrevus (ocrelizumab), a humanized monoclonal antibody developed by Genentech for treating patients with PPMS.
Ocrevus targets B-cells harboring CD20 surface protein (inactive and memory, but not stem or plasma cells). CD20+ B-cells are thought to target axons and myelin sheaths, leading to a series of inflammatory immune responses involved in the pathogenesis of MS and the corresponding disability. A collaboration of university and hospital researchers in Spain conducted a study to determine other immune cells that may be affected by Ocrevus. The multicenter prospective study involved examining B-cell and T-cell subsets in patients with PPMS taking Ocrevus using flow cytometry.
The results showed that Ocrevus lowered memory, naive, and inflammatory cytokine–producing B cells, particularly those producing granulocyte-macrophage colony-stimulating factor, TNF-alpha, and IL-6 and IL-10. Although Ocrevus targets B-cells, CD20+ T cells were also lowered by 6 months of Ocrevus treatment. CD20+ T cells have proinflammatory and migratory properties, factors that may have a significant role in the pathogenesis of MS. Decreases in CD4+ and INF-gamma–producing T cells were also decreased. The observed immune cell reduction accompanied a reduction in serum neurofilament light chain (sNfL) levels, a biomarker for neuroaxonal injury.
Interestingly, Ocrevus treatment affected CD20- T cells by increasing the ratio of naive:effector T cell (favoring naive T cells), indicating a redistribution of the T-cell compartment. Overall, Ocrevus treatment in patients with PPMS leads to effector B-cell depletion and changes in T-cell response, leading to a lower pro-inflammatory profile and decreased sNfL levels. Future studies in a larger patient population would be beneficial in confirming these findings.
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Figueiredo, M. (2021). Ocrevus Targets Pro-inflammatory T-cells, Not Just B-cells, in... Retrieved 19 February 2021, from https://multiplesclerosisnewstoday.com/news-posts/2021/01/19/besides-b-cells-ocrevus-targets-pro-inflammatory-t-cells-in-primary-progressive-multiple-sclerosis-ppms-study-finds/?cn-reloaded=1