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ICAAC 2011: Zinc Finger Gene Therapy Boosts CD4 Cells, May Lower HIV Viral Load


HIV positive people who had their CD4 T-cells altered to delete the CCR5 coreceptor continue to experience sustained CD4 cell increases, and a subset of participants with high levels of modified cells maintained lower viral load during an investigational treatment interruption, researchers reported at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011).

Despite the availability of effective antiretroviral therapy (ART), a cure for HIV remains the holy grail of research. The case of the "Berlin Patient" -- a man who apparently remains free of HIV 5 years after receiving a bone marrow transplant for leukemia from a donor naturally lacking CCR5 -- offered proof-of-concept that a functional cure is possible.

Most strains of HIV use the CCR5 coreceptor, along with the CD4 receptor on the surface of certain T-cells, to enter cells and establish infection. A small percentage of people (about 1% of Northern Europeans) who have a natural genetic variation known as CCR5-delta-32 do not express this coreceptor on their cells, and are therefore protected against HIV infection.

Researchers are studying gene therapy technology that uses a zinc finger nuclease (ZFN) developed by Sangamo BioSciences to cut the CCR5 gene out of CD4 cells, in the hope of making them resistant to HIV, like cells that naturally lack the coreceptor.

Study participants have some of their CD4 T-cells removed and treated with the ZFN. The altered cells -- known as SB-728-T -- are multiplied in a laboratory and infused back into the same patient.

At the Conference on Retroviruses and Opportunistic Infections (CROI) this past March, researchers presented the first data from the Phase 1 study. As reported by study participant Matt Sharp, modified T-cells multiplied in the body and migrated to the gut like normal cells. In addition, most participants experienced sustained CD4 cell increases.

At ICAAC, Ronald Mitsuyasu from UCLA presented further data from 9 participants in the West Coast branch of study who at baseline had suboptimal CD4 cell recovery (< 500 cells/mm3; median 384 cells/mm3) despite undetectable viral load on ART. All were men, the median age was about 50 years, and they had been HIV positive for a median of about 20 years.


  • SB-728-T modified CD4 cells persisted for a median of 337 days, with a maximum of 561 days.
  • Modified T-cells continued to multiply in the body and migrate or "traffic" to the rectal mucosa like normal cells.
  • About 25% of patients' CD4 T-cells showed the CCR5 deletion.
  • All participants had sustained CD4 cell increases (median gain of 163 cells/mm3).
  • Most also had improved CD4/CD8 T-cell ratios.
  • The treatment continued to be well-tolerated, with no unexpected adverse side effects.
  • A majority of adverse events were transient injection site reactions and flu-like symptoms during the first 24 hours following infusion of modified cells.

In a late breaker session Dale Ando from Sangamo reported data from the East Coast branch of the study, run by Carl June and Pablo Tebas of the University of Pennsylvania. In this protocol, 6 participants with CD4 counts > 450 cells/mm3 underwent a 12-week analytic ART interruption starting 4 weeks after receiving SB-728-T modified CD4 cells.


  • Higher levels of circulating modified T-cells with both copies of the CCR5 gene deleted were significantly associated with lower viral load during treatment interruption.
  • 3 of 6 participants with the highest levels of T-cells with the double or biallelic CCR5 deletion experienced viral load declines of 0.8 to >2.0 log during ART interruption.
  • One participant who was CCR5-delta-32 heterozygous -- meaning he had 1 gene copy with the natural CCR5 deletion and 1 normal CCR5 gene -- achieved undetectable viral load during treatment interruption after receiving SB-728-T modified cells.

"The data obtained in our treatment interruption studies are very exciting and represent significant progress toward a 'functional cure' for HIV/AIDS," June said in a press release issued by Sangamo.

Investigator affiliations: Mitsuyasu study: David Geffen School of Medicine at UCLA, Los Angeles, CA; Quest Clinical Research, San Francisco, CA; UCSF School of Med., San Francisco, CA; Sangamo Bioscience Inc., Richmond, CA.

Ando study: Sangamo Biosciences, Richmond, CA; Albert Einstein College of Medicine, Bronx, NY; University of Pennsylvania, Philadelphia, PA.



R Mitsuyasu, J Lalezari, S Deeks, et al. Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4 T-Cells to Aviremic HIV-Infected Subjects with Suboptimal CD4 Counts. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H1-375.

D Ando, WW Tang, D Stein, C June, et al. HAART Treatment Interruption following Adoptive Transfer of Zinc Finger Nuclease (ZFN) Modified Autologous CD4 T-cells (SB-728-T) to HIV-infected Subjects Demonstrates Durable Engraftment and Suppression of Viral Load. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H2-794a.

Other Source

Sangamo BioSciences. Sangamo BioSciences Announces Presentation of Groundbreaking Clinical Data From ZFN Therapeutic for HIV/AIDS at ICAAC 2011. September 8, 2011.