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
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.
Authors
- Catherine M. Bollard (ORCID: https://orcid.org/0000-0001-5140-9090)
- Dennis C. Copertino (ORCID: https://orcid.org/0000-0002-3217-4713)
- Michael D. Keller (ORCID: https://orcid.org/0000-0001-8323-3085)
- Talia M. Mota (ORCID: https://orcid.org/0000-0002-8925-0158)
- Rebecca M. Lynch (ORCID: https://orcid.org/0000-0002-7188-8073)
- Winiffer D. Conce Alberto (ORCID: https://orcid.org/0000-0002-4097-9861)
- Carolina Colli Cruz (ORCID: https://orcid.org/0000-0001-7065-3769)
- Jay Tanna
- Divyesh Kukadiya
- Anushree Datar
- Lynsay MacLaren Ehui
- Zabrina L. Brumme (ORCID: https://orcid.org/0000-0002-8157-1037)
- Danielle Sohai
- Fahmida Hoq
- Patrick J. Hanley (ORCID: https://orcid.org/0000-0002-0102-7892)
- Emily Reynolds (ORCID: https://orcid.org/0000-0002-3546-2622)
- Cecilia M. Motta (ORCID: https://orcid.org/0000-0002-5374-1975)
- R. Brad Jones (ORCID: https://orcid.org/0000-0003-4470-1231)
- Natalie N. Kinloch (ORCID: https://orcid.org/0000-0001-8729-247X)
- Abeer Shibli
- Christopher A. Lazarski (ORCID: https://orcid.org/0000-0001-8917-7280)
- Chase D. McCann (ORCID: https://orcid.org/0000-0002-9178-2110)
- Pamela Chansky
- Anqing Zhang (ORCID: https://orcid.org/0000-0003-3043-8014)
- Andrew Wilson
- Sarah Henn
- Haili Lang
- Tan Thinh Huynh
- Bridget Dwyer
Institutions
- Children's National (US)
- Simon Fraser University (CA)
- George Washington University (US)
- Cornell University (US)
- Whitman-Walker Health (US)
- AIDS Vancouver (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1038/s41467-025-59810-2
- Citations
- 3
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.11
Funders
- American Society of Hematology
- Children's National Hospital
- Michael Smith Health Research BC
- National Institutes of Health
- Canadian Institutes of Health Research
- Office of Nuclear Energy Technologies