BRAF inhibitor treatment of classical hairy cell leukemia allows successful vaccination against SARS-CoV-2.

In classical hairy cell leukemia (HCL), standard treatments including purine analogs achieve a durable response (up to 90%), but lead to severe immunosuppression and long-lasting depletion of CD4 + T lymphocytes. The BRAF inhibitor vemurafenib is effective in HCL, but its use in first-line treatment is restricted to select clinical situations (e.g. active infection). Its impact on immune function or response to vaccines in HCL is unclear. We treated four HCL patients with vemurafenib during the COVID-19 pandemic and monitored immune reconstitution and response to SARS-CoV-2 immunization. All patients responded to HCL treatment with normalization of peripheral blood counts. No severe infections occurred. As an indication of limited immunosuppression by vemurafenib, stable CD4 + and CD8 + T lymphocyte counts and immunoglobulin levels were observed. Three out of four patients received SARS-CoV-2 vaccination (Pfizer-BioNTech) during treatment with vemurafenib. IgG antibody levels against the spike-protein of SARS-CoV-2 were detected (40-818 AE/ml). Our data suggest that vemurafenib has limited effects on cellular and humoral immune function in HCL, which allows for successful SARS-CoV-2 vaccination. These data support the use of BRAF inhibitors during the current pandemic where continued immune response is necessary for minimizing the COVID-19-related risk of non-vaccinated patients.

NMR Characterization of Surface Receptor Protein Interactions in Live Cells Using Methylcellulose Hydrogels.

Interactions of transmembrane receptors with their extracellular ligands are essential for cellular communication and signaling and are therefore a major focus in drug discovery programs. The transition from in vitro to live cell interaction studies, however, is typically a bottleneck in many drug discovery projects due to the challenge of obtaining atomic-resolution information under near-physiological conditions. Although NMR spectroscopy is ideally suited to overcome this limitation, several experimental impairments are still present. Herein, we propose the use of methylcellulose hydrogels to study extracellular proteins and their interactions with plasma membrane receptors. This approach reduces cell sedimentation, prevents the internalization of membrane receptors, and increases cell survival, while retaining the free tumbling of extracellular proteins.