Treatment of SHIV-infected, ART-suppressed rhesus macaques with bispecific HIVxCD3 DART® molecules

Bispecific antibody-derived molecules to target persistent HIV infection

“…Similar results were observed when MGD014 or MGD020 were administered by IV infusion at a dose of 1 mg/kg weekly for 6 weeks to SHIV-infected rhesus monkeys maintained on ART. 49 MGD014 or MGD020 exhibited binding to circulating monkey CD4 + or CD8 + T cells without causing increases in T-cell activation or serum cytokines. However, given alone, the MGD014 or MGD020 treatments did not lead to decreases in persistent virus infection parameters, such as cell-associated viral RNA or time to rebound in viremia following ART interruption.…”

“…These findings demonstrate that low dose administration of the VRC07 x anti-rhesus CD3 molecule resulted in the stimulation of circulating monkey T cells, which differs from that observed when MGD014 or MGD020 were administered to cynomolgus monkeys or SHIV-infected rhesus monkeys on ART. 48 , 49 , 56 Because of the low level of Env-expressing cells in SHIV-infected monkeys maintained on ART, the observed T-cell stimulation seems likely to have resulted from direct activation by the anti-rhesus CD3 arm itself (in monomeric or possibly aggregated forms), rather than to co-engagement of Env-expressing and CD3 + T cells by both arms of the molecule.…”