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

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.

Department

Microbiology, Immunology, and Tropical Medicine

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