Drug Database: SB-728-T

What is SB-728-T?What is SB-728-T?

What is SB-728-T?

SB-728-T is an investigational gene therapy product that is being studied to treat or possibly cure HIV.² Gene therapy is a technique that is used to modify genes in order to treat or prevent disease.

To learn how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How does SB-728-T work?How does SB-728-T work?

How does SB-728-T work?

SB-728-T is an investigational gene therapy product created by changing a gene in immune cells, primarily CD4 T cells. SB-728-T is being studied for its ability to help CD4 cells resist infection by HIV and as a possible strategy to cure HIV.^2,4

One way that HIV enters and infects immune cells is by attaching to a specific protein—called a CCR5 receptor—on the immune cell’s surface. In some people, a natural genetic modification disables the CCR5 receptor. People with this modification are less likely to get infected with the most common strain of HIV. SB-728-T treatment changes the gene responsible for the CCR5 receptor and deactivates the CCR5 receptor. By modifying the CCR5 gene, SB-728-T potentially eliminates one way for the most common type of HIV to infect immune cells.^4-7

Select clinical trials of SB-728-TSelect clinical trials of SB-728-T

Select clinical trials of SB-728-T

Study Names: SB-728-1002; NCT01252641

Phase: 1/2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to assess the safety of a single infusion of SB-728-T and its effect on viral load levels.⁸

Study Names: SB-728-1101; NCT01543152

Phase: 1/2
Status: This study has been completed.
Location: United States and Puerto Rico
Purpose: The purpose of this study was to find out whether administering cyclophosphamide (an FDA-approved drug for treating cancer) before participants received an SB-728-T infusion was safe and could help the CCR5-modified T cells multiply in the body. Investigators also looked at whether SB-728-T could control viral load levels during analytical treatment interruption of ART.^9,10
Selected Study Results: Results published in Molecular Therapy (2015) and through bioRxiv (2021) showed that pretreatment with cyclophosphamide was generally safe and when given at certain dose levels was capable of increasing the survival and growth of CCR5-modified T cells. SB-728-T administration resulted in partial control of viral load levels during an analytical treatment interruption of ART.^11,12
Additional Published Material:

• CROI, 2023: Single infusion of stem like CCR5-modified CD4 T cells provide long-term HIV control

Study Names: TRAILBLAZER; NCT03666871

Phase: 1/2
Status: This study is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of this study is to see whether participants who receive SB-728-T will have a greater reduction in the size of the latent HIV reservoir than participants who receive CD4 cells that are not genetically modified at the CCR5 gene.¹³

Study Names: SB-728mR-1401; NCT02225665

Phase: 1/2
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety of repeated SB-728mR-T infusions that were given to participants who also received cyclophosphamide. (SB-728mR-T is also an SB-728-T gene therapy product.)¹⁴

For more details on the studies listed above, see the Health Professional version of this drug summary.

Other studies on SB-728-T gene therapy have been completed or are ongoing. These include the following Phase 1 trials:

• NCT00842634: A completed trial that evaluated the safety and effects of a single infusion of SB-728-T in individuals with HIV.¹⁵ Results are published in the N Engl J Med (2014).
• SB-728-0902 (NCT01044654): A completed study that evaluated the safety and effectiveness of SB-728-T in participants with HIV who had suboptimal CD4 counts while on ART.⁴ Results are available from bioRxiv (2021) and CROI 2023.
• SB-728mR (NCT02388594): A completed study that evaluated the safety and effectiveness of SB-728mR-T when it was given with and without cyclophosphamide to participants with HIV who were on ART.¹⁶ Results are available from J Clin Invest (2021).
• NCT03617198: A study that is examining the safety and effectiveness of using a genetically modified T cell product to treat people with HIV. This study is ongoing, but not recruiting participants.¹⁷ A summary of findings are available from CROI 2022.
• SB-728-1003 (NCT04201782): A long-term follow-up study of participants who have received SB-728-T or SB-728mR-T in a previous trial. This study does not involve any treatment and is ongoing, but not recruiting participants.¹⁸

What side effects might SB-728-T cause?What side effects might SB-728-T cause?

What side effects might SB-728-T cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the SB-728-1101 (NCT01543152) study described under the previous question, side effects included mild infusion reactions related to SB-728-T, such as low-grade fever and chills. In addition, infusions with SB-728-T were associated with a garlic-like odor.^9,19

Because SB-728-T is still being studied, information on possible side effects of the drug is not complete. As testing of SB-728-T continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying SB-728-T?Where can I get more information about clinical trials studying SB-728-T?

Where can I get more information about clinical trials studying SB-728-T?

More information about SB-728-T-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

1. National Center for Biotechnology Information. PubChem substance record for SID 381129581, SB-728-T, Source: ChemIDplus. Accessed December 27, 2023
2. Treatment Action Group website. Research toward a cure trials. Accessed December 27, 2023
3. Sangamo Therapeutics. Form 10-K (2021 annual report). Accessed December 27, 2023
4. Sangamo Therapeutics. A Phase 1 dose escalation, single dose study of autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases SB-278 in HIV-infected patients who have exhibited suboptimal CD4+ T-cell gains during long-term antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 6, 2010. NLM Identifier: NCT01044654. Accessed December 27, 2023
5. Manjunath N, Yi G, Dang Y, Shankar P. Newer gene editing technologies toward HIV gene therapy. Viruses. 2013;5(11):2748-2766. Accessed December 27, 2023
6. National Institute of Allergy and Infectious Diseases (NIAID) news release, dated March 5, 2014. Genetic modification of cells proves generally safe as HIV treatment strategy. Accessed December 27, 2023
7. Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIVAIDS Rep. 2014;11(1):11-19. Accessed December 27, 2023
8. Sangamo Therapeutics. A Phase 1/2, open label, single infusion study of autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases (SB-728-T) in HIV infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 29, 2010. NLM Identifier: NCT01252641. Accessed December 27, 2023
9. Sangamo Therapeutics. A Phase I, open-label study to assess the effect of escalating doses of cyclophosphamide on the engraftment of SB-728-T in aviremic HIV-infected subjects on HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01543152. Accessed December 27, 2023
10. Baxter Healthcare Corporation. Cyclophosphamide: full prescribing information, March 2017. DailyMed. Accessed December 27, 2023
11. Ando D, Blick G, Lalezari J, et al. A dose escalation study of cyclophophamide (CTX) to enhance SB-728-T engraftment. Mol Ther. 2015;23:S11. Accessed December 27, 2023
12. Zeidan J, Sharma AA, Lee G, et al. Infusion of CCR5 gene-edited T cells allows immune reconstitution, HIV reservoir decay, and long-term virological control. bioRxiv. Published online March 1, 2021:2021.02.28.433290. doi:10.1101/2021.02.28.433290. Accessed December 27, 2023
13. University of Cincinnati. T-cell reinfusion after interfering with lymphocyte binding location of AIDS virus through zinc-finger-nuclease elimination of CCR5 receptors: The TRAILBLAZER Study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 7, 2018. NLM Identifier: NCT03666871. Accessed December 27, 2023
14. Sangamo Therapeutics. A Phase 1/2, open-label study to assess the safety and tolerability of repeat doses of autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases in HIV-infected subjects following cyclophosphamide conditioning. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 22, 2014. NLM Identifier: NCT02225665. Accessed December 27, 2023
15. University of Pennsylvania. A Phase I study of autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases SB-728 in HIV-infected patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 4, 2009. NLM Identifier: NCT00842634. Accessed December 27, 2023
16. University of Pennsylvania. A Phase I study of T-cells genetically modified at the CCR5 gene by zinc finger nucleases SB-728mR in HIV-infected patients, with or without the CCR5 delta-32 mutation, pre-treated with cyclophosphamide. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 24, 2015. NLM Identifier: NCT02388594. Accessed December 27, 2023
17. University of Pennsylvania. A pilot study of T cells genetically modified by zinc finger nucleases SB-728mR and CD4 chimeric antigen receptor in HIV-infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 9, 2018. NLM Identifier: NCT03617198. Accessed December 27, 2023
18. Sangamo Therapeutics. Long-term follow-up of HIV-infected subjects treated with autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases (SB-728-T or SB-728mR-T). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 13, 2019. NLM Identifier: NCT04201782. Accessed December 27, 2023
19. Blick G, Lalezari J, Hsu R, et al. A dose escalation study of cyclophosphamide (CTX) to enhance SB-728-T engraftment. Conference on Retroviruses and Opportunistic Infections; February 23-26, 2015; Seattle, WA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2015. Accessed December 27, 2023