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Florian Klein and colleagues report that treating viremic HIV-1-infected individuals with the broadly neutralizing antibody 10-1074 reduced virus levels in blood, but antibody-resistant virus did emerge.
Allogeneic chimeric antigen receptor (CAR) T cells are capable of inducing graft-versus-host disease (GVHD) in recipients, yet this is not commonly seen in the clinic. Marcel van den Brink, Michel Sadelain and colleagues show that alloreactive CAR T cells have reduced effector function due to signaling through the CAR and T cell receptor, resulting in reduced GVHD, while the graft-versus-leukemia effect is maintained by non-alloreactive CAR T cells.
Loss of the metalloproteinase Adamts1 leads to aortic pathology in mice due to increased NOS2-dependent NO production. Decreased Adamts1 expression, associated with increased NOS2 expression, occurs in Marfan syndrome (MFS) mice and in MFS patients, and NOS2 inhibition prevents and reverses aortic pathology in MFS mice.
The therapeutic response of acute myelogenous leukemia to the nucleoside analog ara-C is controlled by SAMHD1, an enzyme that hydrolyzes the activemetabolite ara-CTP.