Monoclonal antibodies and progressive multifocal leukoencephalopathy

Neoplasm Related Encephalopathies

“…During latency, rearrangements in the NCCR occur leading to the more aggressive, neurotropic prototype JCV. This hypothesis was supported by the intriguing observation of possible latency in B-cells, possessing all the necessary machinery for gene rearrangement (Berger et al, 2009). Moreover, the fact that PML remains a rare entity despite the high prevalence of JCV-infection points towards the necessity of this genetic alteration.…”

“…The difference between these two types is the appearance of rearrangements in the non-coding control region (NCCR) of the virus leading to a neurotropic prototype JCV (Berger et al, 2009). …”

“…Each monoclonal antibody has its specific immunomodulatory characteristics (Berger et al, 2009) possibly providing the reason why some monoclonal antibodies are more frequently associated with PML than others. In addition, the disorder requiring immunomodulatory therapy can also be a predisposing condition for developing PML making it difficult to assess the real influence of the therapy on the incidence of PML.…”

“…Berger et al, 2009 andWeissert, 2011). Diagnoses of PML in patients treated with efalizumab for psoriasis or with rituximab for lymphoproliferative disorders followed but to a lesser extent than natalizumab.…”

Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody–drug Conjugate

“…28 Efalizumab, a humanized αCD11a antibody, was developed and approved by FDA for treating psoriasis, but was withdrawn from the market due to severe side effects, including bacterial sepsis, viral meningitis, and progressive multifocal leukoencephalopathy. 29,30 As integrins play important roles in leukocyte trafficking, reduction of surface expression of CD11a due to antibody-mediated receptor internalization may significantly impair the immune cell function and attribute to the immunosuppressing phenotype. Similar to the literature report, 22 we also observed that upon binding and internalization of the αmuCD11a antibody, the surface expression of CD11a on T cells, but not monocytes, macrophages, or neutrophils, were dramatically impaired in the spleen, lymph node and blood (Figure 6d,e, Supplementary Figures S4C, D and S5C, D).…”