Presentation Abstract

Session: 042-New Therapies for HIV and HCV
Saturday, Sep 17, 2011, 4:00 PM - 6:30 PM
Presentation Title: H1-375 - Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4 T-Cells to Aviremic HIV-Infected Subjects with Suboptimal CD4 Counts
Location: W179b
Presentation Number: H1-375
Pres. Time: Saturday, Sep 17, 2011, 5:00 PM - 5:15 PM
Category: H2
Keywords: CCR5 ; HIV-therapy 
Author(s): R. Mitsuyasu, MD - Professor of Medicine1, J. Lalezari, MD - Director 2, S. Deeks, MD - Professor of Medicine 3, W. W. Tang, MD - VP, Clinical Research 4, S. Wang, MD - Director, Clinical Research 4, G. Lee, PhD - Research Scientist 4, M. Giedlin, PhD - Vice President 4, M. Holmes, PhD - Senior Director 4, P. Gregory, PhD - Chief Scientific Officer 4, D. Ando, MD - Chief Medical Officer 4;
1David Geffen Sch. of Med. at UCLA, Los Angeles, CA, 2Quest Clinical Res., San Francisco, CA, 3UCSF Sch. of Med., San Francisco, CA, 4Sangamo Bioscience Inc., Richmond, CA.
Financial Disclosures:  R. Mitsuyasu,
Sangamo Biosciences Inc Role(s): Investigator, Other, Received: Research Support.
Janssen Role(s): Investigator, Received: Research Support.
J. Lalezari,
Sangamo Biosciences Inc Role(s): Investigator, Received: Research Support.
S. Deeks,
Sangamo Biosciences Inc Role(s): Investigator, Received: Research Support.
W. W. Tang,
Sangamo Bioscience Role(s): Employee, Received: Salary.
S. Wang,
Sangamo Biosciences Inc Role(s): Employee, Received: Salary.
G. Lee,
Sangamo Biosciences Role(s): Employee, Received: Salary.
M. Giedlin,
Sangamo Biosciences Role(s): Employee, Received: Salary.
M. Holmes,
Sangamo Biosciences Role(s): Employee, Received: Salary.
P. Gregory,
Sangamo Bioscience Role(s): Employee, Received: Salary.
D. Ando,
Sangamo Bioscience Role(s): Employee, Received: Salary.
Abstract: Background: Immune reconstitution remains an issue for aviremic HIV patients who, despite HAART, have low CD4 counts. We have previously reported preliminary data on the sustained adoptive transfer of SB-728-T to aviremic HIV subjects. We report completion of enrollment of this Phase 1 study and data relating to safety, increases in CD4 cells, SB-728-T persistence and homing to gut mucosa. Methods: Nine aviremic HIV+ subjects with CD4 counts between 200-500 cells/mm3 were enrolled into 3 cohorts that received 10, 20 and 30 billion total cells, respectively. SB-728-T was manufactured with a mean CCR5 modification of 25+6%. After reinfusion, subjects were followed weekly for 1 mo and then monthly for 11 mos. Results: The median duration of follow-up for all subjects is 218 days (22-366). Data (mean+SD) through Day 28 are available on the first 8 subjects. SB-728-T infusion was well tolerated with only mild reversible infusion related AEs. Peripheral blood CD4 cell counts increased by 216+192 cells/mm3 at D28 (range -19 to 617) with restoration of normal CD4/CD8 ratios in 4 of the 7 subjects with abnormal baseline ratios. SB-728-T as measured by nested PCR ranged from 0.2 to 2.8% of PB CD4 cells at D28 and persisted for the duration of follow-up. SB-728-T was detected in the rectal mucosa of the first 6 subjects at D14 and constituted up to 6% of total mucosal CD4 cells at D90. Conclusions: SB-728-T infusion in HIV infected subjects is well tolerated. Sustained increases in CD4 cells were seen in all subjects. SB-728-T was detected at frequencies up to 5.5-fold higher than predicted suggesting expansion of these cells. The level of gene marking is approximately 1-log greater than in previous CD4 T cell adoptive transfer studies. SB-728-T distributes normally to the gut mucosa and increased over time. These preliminary data suggest that SB-728-T offers the potential to reconstitute the immune system in HIV patients.




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