Drugs

SB-728-T

SB-728-T

Other Names: CCR5-ZFN, CCR5-specific zinc finger protein nuclease, SB-728, SB-728mR modified T cells, SB-728mR-T Drug Class: Gene Therapy Products Registry Number: S900006290 (ChemID) Organization: Sangamo Therapeutics Phase of Development: SB-728-T is in Phase I/II development for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group website,2 Viruses article,3 and Sangamo Therapeutics website4)

What is SB-728-T?

What is SB-728-T?

SB-728-T is an investigational gene therapy product.2 Gene therapy is an experimental technique that uses short sections of genetic material to treat or prevent disease. SB-728-T is being studied for its ability to help CD4 cells survive during HIV infection and as a possible strategy to cure HIV.3,5–9

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

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.2,5

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.3,5,10–12

Which clinical trials are studying SB-728-T?

Which clinical trials are studying SB-728-T?

Study Names: SB-728-0902; NCT01044654
Phase: I
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to look at the safety and effectiveness of intravenous infusions of SB-728-T in people with HIV.5,6,13

Study Names: SB-728-1101; NCT01543152
Phase: I/II
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 modified cells multiply in the body. Investigators also looked at whether SB-728-T could control viral load levels during a treatment interruption of ART.7

Study Names: TRAILBLAZER; NCT03666871
Phase: I/II
Status: This study is not yet recruiting.
Location: Not available
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 unmodified CD4 cells.14

Study Names: SB-728mR-1401; NCT02225665
Phase: I/II
Status: This study is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the safety of repeated SB-728mR-T infusions that are given to participants who have also received cyclophosphamide. (SB-728mR-T is also an SB-728-T gene therapy product.)9,15

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 currently recruiting participants. These include the following Phase I studies:

  • NCT02388594: This ongoing study is evaluating the safety and effectiveness of SB-728mR-T when it is given with and without cyclophosphamide in participants with HIV who are on ART.8
  • NCT03617198: This study is examining the safety and effectiveness of using a modified T cell product to treat people with HIV. This study is currently recruiting participants.16
  •  

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. The following side effects were observed in some of the studies of SB-728-T listed above.

SB-728-0902 (NCT01044654):
In this Phase I study, participants reported having some side effects related to SB-728-T infusion, but these side effects were mild and reversible.5,17

SB-728-1101 (NCT01543152):
In this Phase I/II study, mild infusion reactions related to SB-728-T, such as low-grade fever and chills, were reported. In addition, infusions with SB-728-T were associated with a garlic-like odor.7,18

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?

More information about SB-728-T-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

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 information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: SB-728-T. https://chem.nlm.nih.gov/chemidplus/sid/s900006290. Accessed December 13, 2018.
  2. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed December 13, 2018.
  3. Manjunath N, Yi G, Dang Y, Shankar P. Newer gene editing technologies toward HIV gene therapy. Viruses. 2013;5(11):2748-2766.
  4. Sangamo Therapeutics website. HIV. Pipeline: Therapeutic Programs Under Development. https://www.sangamo.com/pipeline. Accessed December 13, 2018.
  5. 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 December 13, 2018.
  6. 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 December 13, 2018.
  7. 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 December 13, 2018.
  8. 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 December 13, 2018.
  9. 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 December 13, 2018.
  10. National Institute of Allergy and Infectious Diseases (NIAID). News release: genetic modification of cells proves generally safe as HIV treatment strategy.https://www.niaid.nih.gov/news-events/genetic-modification-cells-proves-generally-safe-hiv-treatment-strategy. Published March 5, 2014. Accessed December 13, 2018.
  11. 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 December 13, 2018.
  12. Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIVAIDS Rep. 2014;11(1):11-19.
  13. Zeidan J, Lee G, Lalezari J, et al. Host immune environment significantly impact the level of CD4 reconstitution and the effects on latent reservoir in HIV subjects receiving ZFN CCR5 modified CD4 T-cells (SB-728-T). Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver CO. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. http://www.natap.org/2013/ICAAC/ICAAC_57.htm. Accessed December 13, 2018.
  14. 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 December 13, 2018.
  15. Sangamo Therapeutics. Press Release: Sangamo BioSciences ZFP therapeutic program in HIV/AIDS featured at three major scientific conferences in October 2014.https://www.prnewswire.com/news-releases/sangamo-biosciences-zfp-therapeutic-program-in-hivaids-featured-at-three-major-scientific-conferences-in-october-2014-279399672.html. Published October 16, 2014. Accessed December 13, 2018.
  16. 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 December 13, 2018.
  17. Mitsuyasu R, Lalezari J, Deeks S, et al. Adoptive transfer of zinc finger nuclease (ZFN) modified autologous CD4 T-cells to aviremic HIV-infected subjects with suboptimal CD4 counts. Abstract presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2011; Chicago, IL. Abstract H1-375. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d4df5ac5-0855-47ac-9c87-f2c16aaeb7a9&cKey=72e47ff3-2053-458c-8d9c-3d32c27184a9&mKey=%7b0C918954-D607-46A7-8073-44F4B537A439%7d. Accessed December 13, 2018.
  18. 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 December 13, 2018.

Last Reviewed: December 14, 2018