CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/AIDS
Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIVCAR T cells) may provide a safe and effective way to eliminate HIV-infected cells. However, the number of HIV-infected cells is low in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of HIV-1-infected individuals are CMV-seropositive and CMV-specific T cells have been shown to persist. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human Phase 1, open-label, single-arm study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH), and achieve long-term remission in the presence of ART.
Conditions:
🦠 HIV-1
🗓️ Study Start (Actual) 30 July 2024
🗓️ Primary Completion (Estimated) 11 December 2026
✅ Study Completion (Estimated) 11 December 2026
👥 Enrollment (Estimated) 15
🔬 Study Type INTERVENTIONAL
📊 Phase EARLY_PHASE1
Locations:
📍 Duarte, California, United States
📍 San Diego, California, United States

📋 Eligibility Criteria

Description

    Inclusion Criteria:

    • * Participant must be ≥ 18 years of age at the time of screening;
    • * Karnofsky Performance Status (KPS) ≥ 70;
    • * Documented HIV-1 infection anytime prior to study entry.;
    • * On stable ART with undetectable HIV-1 RNA (i.e \< 20 copies /mL) for at least 48 weeks prior to screening (2 plasma HIV-1 RNA blips 25-200 copies/mL are allowable);
    • * CD4+ cell count ≥ 450 cells/μL;
    • * Adequate organ function;
    • * Willingness to interrupt ART regimen for 4 days prior to leukapheresis;
    • * Not pregnant or breastfeeding.

    Exclusion Criteria:

    • * Concurrent illness or comorbid condition;
    • * History of resistance to two or more classes of antiretroviral drugs;
    • * History of prior receipt of an experimental HIV-1, immunotherapeutic agent, or gene therapy product.
Ages Eligible for Study: 18 Years to N/A (ADULT, OLDER_ADULT)
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: Yes

🗓️ Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

  • First Submitted 1 February 2024
  • First Submitted that Met QC Criteria 1 February 2024
  • First Posted 9 February 2024

Study Record Updates

  • Last Update Submitted that Met QC Criteria 18 June 2024
  • Last Update Posted 21 June 2024
  • Last Verified June 2024