Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells
Fig 6
HIVxCD3 DARTs reduce ex vivo HIV expression in PBMCs isolated from HIV-infected participants on suppressive cART.
(A-B) Resting Model: Unstimulated PBMCs from 4 HIV-infected participants on suppressive cART were cultured with 400 pM of a DART combination (200 pM each of PGT121xCD3 and 7B2xCD3) or 400 pM of RSVxCD3. Supernatant HIV RNA was quantitated on Day 8 (A) and Day 14 (B). By Day 14, statistically significant reduction in vRNA level was observed in 3 out of 4 participants treated with the HIVxCD3 DART combination, but not with control DART compared to no DART (*p<0.05, **p<0.005, 2-tailed Mann-Whitney U-Test). Horizontal bars represent the medians for each group. (C) PKC Agonist-Inducible Model. PBMCs from 4 HIV-infected participants on suppressive cART were cultured untreated or treated with 1 μM indolactam, a PKC agonist, and with or without an HIVxCD3 DART combination (200 pM PGT121xCD3 + 200 pM 7B2xCD3) or control RSVxCD3 DART (400 pM). After 7 days of incubation, total CD4 T cells were isolated from PBMCs and re-stimulated with 1 μM indolactam. After an additional 3 days of incubation, supernatant HIV RNA was quantitated. In 2 out of 4 participants, HIVxCD3 DARTs significantly reduced the indolactam-induced vRNA vs. control DART or no DART (**p<0.005, *p<0.05, 2-tailed Mann-Whitney U-Test). Horizontal bars represent the medians for each group.