CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/AIDS

Last updated: February 17, 2025
Sponsor: City of Hope Medical Center
Overall Status: Active - Recruiting

Phase

1

Condition

N/A

Treatment

CMV/HIV-CAR T Cells

Clinical Study ID

NCT06252402
22508
  • Ages > 18
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

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.

Eligibility Criteria

Inclusion

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 48weeks 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

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 genetherapy product.

Study Design

Total Participants: 15
Treatment Group(s): 1
Primary Treatment: CMV/HIV-CAR T Cells
Phase: 1
Study Start date:
December 19, 2024
Estimated Completion Date:
December 11, 2026

Study Description

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 (HIV-CAR T cells) may provide a safe and effective way to eliminate HIV-infected cells. However, HIV-infected cells in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of individuals with HIV-1 are CMV-seropositive and CMV-specific T cells have been shown to persist at high frequency due to CMV antigen stimulation. 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, open-label, single-arm, pilot 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). Based on the results of this safety study, CMV vaccine and analytic treatment interruption will be evaluated with the CMV/HIV-CAR T cell investigational product in a subsequent protocol.

The trial is a first-in-human, pilot study to evaluate the feasibility and safety and determine the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of CMV/HIV-CAR T cells in PLWH. Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cell manufacturing. Participants will resume their ART regimen immediately after leukapheresis. If the manufacturing is not successful, a second apheresis may be scheduled no sooner than 3 weeks later with temporary interruption of ART regimen for 4 days prior to leukapheresis. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV) infusion of autologous CMV/HIV-CAR T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cells may be explored.

Connect with a study center

  • City of Hope Medical Center

    Duarte, California 91010
    United States

    Active - Recruiting

  • UCSD, Division of Infectious Diseases and Global Public Health

    San Diego, California 92093
    United States

    Active - Recruiting

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