Repurposing a protease inhibitor for COVID-19; plus City of Hope’s scorpion venom CAR T and Blaze’s tech for tissue-targeted steroid delivery

Camostat mesylate, a TMPRSS2 inhibitor already approved in Japan for digestive system indications, has become one of the latest drugs that could be repurposed to treat COVID-19. A team led by Leibniz Institute for Primate Research researchers confirmed Thursday in Cell hypotheses that -- like severe acute respiratory syndrome coronavirus (SARS-CoV) -- SARS-CoV-2 viral fusion in cultured cells is facilitated by TMPRSS2 cleavage of the viral spike following the spike’s binding of ACE2. They also showed that camostat mesylate prevented SARS-CoV-2 spike from entering cultured lung cells and other cell types.

A City of Hope team has developed a chlorotoxin-based chimeric antigen receptor) that could expand the glioblastoma patient populations who could benefit from CAR T therapy. Described in a Science Translational Medicine article published Wednesday, the CAR’s tumor-targeting domain consists of chlorotoxin, a scorpion venom peptide known to bind glioblastoma cells, in lieu of a traditional tumor-targeting antibody sequence. In mice, intratumoral injection of chlorotoxin CAR T cells increased survival and led to regression of glioblastoma tumors expressing low levels of HER2, EGFR and IL13RA2, glioblastoma antigens than have been targeted in the clinic by traditionally designed CAR Ts. The team also identified tumor MMP2 acted as the chlorotoxin CAR’s primary target. The institute is recruiting patients for a Phase I trial of a chlorotoxin-based CAR T therapy for glioblastoma...