Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

BACKGROUND REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS We randomly assigned, in a 1:1 ratio, participants (=12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARSCoV- 2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase- quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load

Effect of dasatinib against thyroid cancer cell lines in vitro and a xenograft model in vivo

Tyrosine kinase inhibitors (TKIs) have emerged as a promising class of agents against thyroid cancer. The aim of the present study was to investigate the in vitro and in vivo activity of dasatinib against a panel of thyroid cancer cell lines and explore possible mechanisms of action, using various assays and western blotting. Our results showed that dasatinib exhibits prominent cytostatic activity both in vitro and in vivo against thyroid cancer cell lines with RET/PTC rearrangement (BHP2-7) and KRAS mutation (Cal62). Although dasatinib has primarily been described as an ABL/SRCfamily kinase inhibitor, the cytostatic activity observed in the present study is mediated by several off-target effects of dasatinib, some of which have not previously been reported. These effects include a reduction in phospho-FAK, FAK, RAS, Caveolin and SYK protein levels and an increase in β-catenin protein expression, which leads to the induction of senescence, an increase in the adhesiveness of the cells, a decrease in reactive oxygen species level, and changes in the expression profile of molecules involved in cellular adhesion such as integrins. Therefore, we propose that dasatinib is an effective therapeutic agent for certain patients with thyroid cancer, and these candidate patients may be identifiable on the basis of standard genotypic analyses

Off-target effects of c-MET inhibitors on thyroid cancer cells

10.1158/1535-7163.MCT-13-0187Molecular Cancer Therapeutics131134-143MCTO