Major advances in the treatment of multiple myeloma in American Society of Hematology annual meeting 2020.

Treatment of multiple myeloma (MM) has advanced dramatically in the past two decades. However, under the conditions of the COVID-19 pandemic, treatment strategies have been modified accordingly. Numerous novel agents, updated trials, and major advances in myeloma have been reported in the American Society of Hematology 2020 annual meeting, either for transplant-eligible or ineligible patients. Hot topics such as the significance of autologous stem cell transplantation (ASCT), development of novel agents, and chimeric antigen receptor-T (CAR-T) cells have been widely discussed. The triplet regimen bortezomib, lenalidomide, and dexamethasone (VRd) is recommended as the standard first-line treatment, and the addition of a fourth drug improves efficacy and survival. The value of ASCT remains undoubtful, even in the era of quadruplet induction. Dual-drug maintenance, including proteasome inhibitors and immunomodulatory drugs, overcomes unfavorable outcomes in high-risk patients. For relapsed/refractory myeloma (RRMM) patients, novel agents such as selinexor and venetoclax are superior. CAR-T cells and other cell-surface-targeted therapies also appear promising.

Isolation of a human monoclonal antibody specific for the receptor binding domain of SARS-CoV-2 using a competitive phage biopanning strategy.

The infection of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 200 000 deaths, but no vaccine or therapeutic monoclonal antibody is currently available. SARS-CoV-2 relies on its spike protein, in particular the receptor-binding domain (RBD), to bind human cell receptor angiotensin-converting enzyme 2 (ACE2) for viral entry, and thus targeting RBD holds the promise for preventing SARS-CoV-2 infection. In this work, a competitive biopanning strategy of a phage display antibody library was applied to screen blocking antibodies against RBD. High-affinity antibodies were enriched after the first round using a standard panning process in which RBD-His was immobilized as a bait. At the next two rounds, immobilized ACE2-Fc and free RBD-His were mixed with the enriched phage antibodies. Antibodies binding to RBD at epitopes different from ACE2-binding site were captured by the immobilized ACE2-Fc, forming a "sandwich" complex. Only antibodies competed with ACE2 can bind to the free RBD-His in the supernatant and be subsequently separated by the nickel-nitrilotriacetic acid magnetic beads. rRBD-15 from the competitive biopanning of our synthetic antibody library, Lib AB1, was produced as the full-length IgG1 format. It was proved to competitively block the binding of RBD to ACE2 and potently inhibit SARS-CoV-2 pseudovirus infection with IC50 values of 12 nM. Nevertheless, rRBD-16 from the standard biopanning can only bind to RBD in vitro, but not have the blocking or neutralization activity. Our strategy can efficiently isolate the blocking antibodies of RBD, and it would speed up the discovery of neutralizing antibodies against SARS-CoV-2.