Wang, Wen

ABSTRACT Contezolid has activity against methicillin-resistant Staphylococcus aureus (MRSA), a common cause of orthopedic infection. In a rat model of foreign body osteomyelitis, 1.3 log 10 cfu/g bone and 0.5 log 10 cfu/k-wire reduction in MRSA was found in tibiae ( P = 0.0186) and K-wires, respectively, of contezolid-treated compared to untreated rats. No MRSA was recovered from animals receiving rifampin alone or in combination with contezolid or vancomycin. There was no emergence of resistance to contezolid, vancomycin, or rifampin.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8 + CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.