Autologous HIV-specific T cell therapy targeting conserved epitopes is well-tolerated in six adults with HIV: an open-label, single-arm phase 1 study

Authors

• Danielle K. Sohai, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Michael D. Keller, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Patrick J. Hanley, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Fahmida Hoq, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Divyesh Kukadiya, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Anushree Datar, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Emily Reynolds, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Dennis C. Copertino, Infectious Diseases Division, Department of Medicine, Weill-Cornell Medicine, New York, NY, USA.
• Christopher Lazarski, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Chase D. McCann, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Jay Tanna, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Abeer Shibli, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Haili Lang, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Anqing Zhang, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Pamela A. Chansky, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Cecilia Motta, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Tan T. Huynh, Infectious Diseases Division, Department of Medicine, Weill-Cornell Medicine, New York, NY, USA.
• Bridget Dwyer, Integrated Biomedical Sciences, Department of Microbiology, Immunology, and Tropical Medicine, and Department of Pediatrics, The George Washington University, Washington, DC, USA.
• Andrew Wilson, Integrated Biomedical Sciences, Department of Microbiology, Immunology, and Tropical Medicine, and Department of Pediatrics, The George Washington University, Washington, DC, USA.
• Rebecca Lynch, Integrated Biomedical Sciences, Department of Microbiology, Immunology, and Tropical Medicine, and Department of Pediatrics, The George Washington University, Washington, DC, USA.
• Talia M. Mota, Infectious Diseases Division, Department of Medicine, Weill-Cornell Medicine, New York, NY, USA.
• Winiffer D. Conce Alberto, Infectious Diseases Division, Department of Medicine, Weill-Cornell Medicine, New York, NY, USA.
• Zabrina L. Brumme, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
• Natalie N. Kinloch, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
• Conrad Russell Cruz, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA.
• Lynsay MacLaren Ehui, Whitman-Walker Health, Washington, DC, USA.
• Sarah Henn, Whitman-Walker Health, Washington, DC, USA.
• R Brad Jones, Infectious Diseases Division, Department of Medicine, Weill-Cornell Medicine, New York, NY, USA.
• Catherine M. Bollard, Center for Cancer and Immunology Research, and Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, USA. cbollard@childrensnational.org.

Document Type

Journal Article

Publication Date

5-15-2025

Journal

Nature communications

Volume

16

Issue

1

DOI

10.1038/s41467-025-59810-2

Abstract

Novel cellular therapies may enable HIV control or cure. HIV-specific T cells targeting conserved immunogenic protein regions of HIV Gag/Pol and the entirety of HIV Nef, termed HST-NEETs, eliminate HIV infected cells in vitro. Here we enroll seven participants in an open-label, single-arm phase 1 study (NCT03485963) to evaluate the safety (primary endpoint) of two autologous administrations of HST-NEET products without prescribed lymphodepletion. Adults with well-controlled HIV on anti-retroviral therapy are eligible. Six participants completed safety monitoring. No serious product-related toxicities are observed. Secondary endpoints are to assess expansion and persistence of HIV-reactive T cell clones, and changes to the HIV reservoir for each infused participant. HIV-specific T cell and HIV anti-Env antibody responses increase in two participants after infusion two. A trend towards decreasing levels of intact proviruses is observed in 2 participants. Three participants show persistence of HIV-reactive, product-associated T cell clones for ≥40 weeks post infusions. HST-NEETs infusions are well-tolerated. Future trials are needed to evaluate the efficacy of HST-NEETs in this population.

APA Citation

Sohai, Danielle K.; Keller, Michael D.; Hanley, Patrick J.; Hoq, Fahmida; Kukadiya, Divyesh; Datar, Anushree; Reynolds, Emily; Copertino, Dennis C.; Lazarski, Christopher; McCann, Chase D.; Tanna, Jay; Shibli, Abeer; Lang, Haili; Zhang, Anqing; Chansky, Pamela A.; Motta, Cecilia; Huynh, Tan T.; Dwyer, Bridget; Wilson, Andrew; Lynch, Rebecca; Mota, Talia M.; Conce Alberto, Winiffer D.; Brumme, Zabrina L.; Kinloch, Natalie N.; Cruz, Conrad Russell; MacLaren Ehui, Lynsay; Henn, Sarah; Brad Jones, R; and Bollard, Catherine M., "Autologous HIV-specific T cell therapy targeting conserved epitopes is well-tolerated in six adults with HIV: an open-label, single-arm phase 1 study" (2025). GW Authored Works. Paper 7254.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7254

Department

Microbiology, Immunology, and Tropical Medicine