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Author Topic: Functional Control of Viremia in CCR5-Δ32 Heterozygous ...  (Read 1455 times)

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Offline greenbean

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  • Posts: 23
Functional Control of Viremia in CCR5-Δ32 Heterozygous ...
« on: September 10, 2013, 07:55:38 PM »
Sangamo's late breaker at ICAAC.
Highlight: one patient went undetectable for over 4 weeks after the infusion and still ongoing.

Looks promising

Functional Control of Viremia in CCR5-Δ32 Heterozygous
(Δ32HZ) HIV+ Subjects Following Adoptive Transfer of Zinc Finger
Nuclease CCR5 Modifi ed Autologous CD4 T-cells (SB-728-T)
D. Ando1
, J. Lalezari2
, G. Blick3
, J. Rodriquez4
, R. Hsu5
, T. Hawkins6
, D. Parks7
, j.
, R-P. Sekaly8
, S. Deeks9
; 1
Sangamo, Richmond, CA, 2
Quest, SF, CA, 3
Norwalk, CT, 4
PC, NY, NY, 6
SWC, S Fe, NM, 7
Louis, MO, 8
Background: Expression of CCR5 by CD4 cells is necessary for productive R5
HIV infection. Biallelic KO of CCR5 in CD4 cells by SB-728-T is enhanced in
CCR5 Δ32HZ. This study was undertaken to assess the effect of SB-728-T on
Δ32HZ, following an earlier report of a SB-728-T-treated Δ32HZ whose VL
became undetectable (UD) at the end of a treatment interruption (TI). Methods:
Ten aviremic, HIV+, Δ32HZ on stable ART with CD4 counts >500/mL were
enrolled. SB-728-T was manufactured with a mean CCR5 modifi cation of 25.5%
(range 17.4-44%). Subjects received 16.2+4.2 (mean+SD) billion total cells (range
9.0-23.5). After infusion, subjects were followed for 8 wks and then underwent a 16
week TI. Results: Median duration of follow-up for all subjects is 305 days (range
70-365). Circulating total CD4 counts increased from baseline by 1156+601 cells/
mLat D28. Estimated biallelic modifi ed CD4 cells ranged from 5 to 14% of PBMC
CD4 cells at D28. Three subjects had X4/R5 at baseline and in 2 R5 subjects, TI
was terminated early per protocol due to high initial VL. One R5 subject recently
commenced TI. Of the 4 remaining R5 subjects, 1 showed no signifi cant VL
reduction from peak during TI. One subject had a 1-log VL reduction; and another
subject showed a persistent 1-log reduction from peak with a single UD VL before
resuming HAART. Both of these subjects had increased polyfunctional GAG T
cell responses. The 4th subject has UD VL persisting for 4 weeks following an
initial peak; TI is ongoing. The two subjects with UD VL during TI had low HIV
set points (VL 3-4000 copies/mL) and proviral DNA(<100 copies/106
 PBMC by
ddPCR). Conclusions: Adoptive transfer of SB-728-T in Δ32HZ resulted in VL
reductions from peak levels during TI in 3 of 4 subjects with 2 subjects having
UD levels, persisting in one subject for 4 weeks at the time of abstract submission.
Reductions in VL were associated with low baseline HIV reservoir, low HIV
setpoint, and increases in polyfunctional GAG T-cell responses. CCR5 knockout in
CD4 T cells by biallelic ZFN-mediated CCR5 modifi cation may lead to functional
control of R5 HIV infection in a subset of CCR5 delta32 HZ individuals.


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