SB-728-T is in Phase 1/2 development for HIV treatment.
(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group website,2 and Viruses article3)
What is SB-728-T?
SB-728-T is an investigationalproduct that is being studied to treat or possibly cure HIV.2 therapy is a technique that is used to modify genes in order to treat or prevent disease.3
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.2,4 SB-728-T is being studied for its ability to help CD4 cells survive during HIVand as a possible strategy to cure HIV.4-8
One way that HIV enters and infects immune cells is by attaching to a specific—called a —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 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.3,4,9-11
Which clinical trials are studying SB-728-T?
Study Names: SB-728-1101; NCT01543152
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- for treating cancer) before participants received an SB-728-T was safe and could help the CCR5-modified T cells multiply in the body. Investigators also looked at whether SB-728-T could control levels during a of ART.6,12,13
Study Names: TRAILBLAZER; NCT03666871
Status:This study is currently 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 than participants who receive CD4 cells that are not genetically modified at the CCR5 gene.14
Study Names: SB-728mR-1401; NCT02225665
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.)8
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 planned. These include the following Phase 1 studies:
- SB-728-0902 (NCT01044654): This is 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
- SB-728mR (NCT02388594): This completed study 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.7
- NCT03617198: This study is examining the safety and effectiveness of using a genetically modified T cell product to treat people with HIV. This study is currently recruiting participants.15
- SB-728-1003 (NCT04201782): This is a long-term follow-up study of participants who have received SB-728-T or SB-728mR-T in a previous trial and completed 3 years of post-infusion follow-up. This study does not involve any treatment. This study has been enrolling by invitation.16
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.6,17
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?
More information about SB-728-T-relatedresearch studies is available from ClinicalTrials.gov.
Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a NIH Clinical Research Trials and You.is right for you. For more information, visit
- United States National Library of Medicine. ChemIDplus Advanced: SB-728-T. https://chem.nlm.nih.gov/chemidplus/sid/s900006290. Accessed July 30, 2020
- Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed July 30, 2020
- Manjunath N, Yi G, Dang Y, Shankar P. Newer gene editing technologies toward HIV gene therapy. Viruses. 2013;5(11):2748-2766.
- 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. https://clinicaltrials.gov/ct2/show/NCT01044654. Accessed July 30, 2020
- Ando D. Functional control of viremia in CCR5-Δ32 heterozygous (Δ32HZ) HIV subjects following adoptive transfer of zinc finger nuclease CCR5 modified autologous CD4 T-cells (SB-728-T). Annual Meeting of the European Society of Gene and Cell Therapy (ESGCT and SETGyC Collaborative Congress); October 25-28, 2013; Madrid, Spain. National AIDS Treatment Advocacy Project (NATAP): HIV Articles. http://www.natap.org/2013/HIV/103013_01.htm. Accessed July 30, 2020
- 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 viremic HIV-infected subjects on HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01543152. https://clinicaltrials.gov/ct2/show/NCT01543152. Accessed July 30, 2020
- 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. https://clinicaltrials.gov/ct2/show/NCT02388594. Accessed July 30, 2020
- 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 ginger 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. https://clinicaltrials.gov/ct2/show/NCT02225665. Accessed July 30, 2020
- National Institute of Allergy and Infectious Diseases. Genetic Modification of Cells Proves Generally Safe as HIV Treatment Strategy. ClinicalInfo. Accessed July 19, 2019. https://aidsinfo.nih.gov/news/1433/genetic-modification-of-cells-proves-generally-safe-as-hiv-treatment-strategy. Accessed July 30, 2020
- Sheehy J, Zack J, Kiem HP, Handibode J. Cell/gene therapy—HIV cure research training curriculum. Located on the AVAC website (http://www.avac.org/cure-curriculum/module3), under PowerPoint. http://www.avac.org/sites/default/files/u16/Gene_Cell_Therapy_July.pptx. Accessed July 30, 2020
- Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIVAIDS Rep. 2014;11(1):11-19.
- Baxter Healthcare Corporation. Cyclophosphamide: full prescribing information, March 2017. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid = 6bae5c14-9e87-4fb6-ae9c-4d875c1ecffe. Accessed July 30, 2020
- Sangamo Therapeutics: Press Release, dated February 26, 2015. Sangamo BioSciences presents new clinical data at CROI 2015 from trial of ZFP Therapeutic® designed to provide functional control of HIV. https://investor.sangamo.com/news-releases/news-release-details/sangamo-biosciences-presents-new-clinical-data-croi-2015-trial. Accessed July 30, 2020
- Case Western Reserve University. 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. https://clinicaltrials.gov/ct2/show/NCT03666871. Accessed July 30, 2020
- University of Pennsylvania. A pilot study of T cells genetically modified by zinc finger nucleases SB-728mR, C34-peptide conjugated to the CXCR4 N-terminus, 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. https://clinicaltrials.gov/ct2/show/NCT03617198. Accessed July 30, 2020
- 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. https://clinicaltrials.gov/ct2/show/record/NCT04201782. Accessed July 30, 2020
- 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. http://www.natap.org/2015/CROI/croi_81.htm. Accessed July 30, 2020
Last Reviewed: July 30, 2020