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

A Pilot Study to Evaluate the Feasibility and Safety of Cytomegalovirus-Specific, Anti-HIV Chimeric Antigen Receptor (CMV-HIV CAR) T Cells in People Living With HIV

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.

Study Overview

• Status: Recruiting
• Conditions: HIV-1
• Intervention / Treatment: Biological: CMV/HIV-CAR T Cells

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Marvin Hanashiro; Phone Number: (619) 543-3740; Email: mhanashiro@health.ucsd.edu
• Study Contact Backup: Name: Steven Hendrickx; Phone Number: (619) 543-6968; Email: smhendrickx@health.ucsd.edu

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Medical Center
      • Principal Investigator: John H. Baird, MD
    • San Diego, California, United States, 92093
      • Recruiting
      • UCSD, Division of Infectious Diseases and Global Public Health
      • Principal Investigator: David Smith, MD
      • Contact: David Smith, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level -1; EGFR+ T Cell Dose (Day 0) 5 x 10^6 cells	Biological: CMV/HIV-CAR T Cells; 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 cewll manufacturing. 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-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.
Experimental: Dose Level +1; EGFR+ T Cell Dose (Day 0) 25 x 10^6 cells	Biological: CMV/HIV-CAR T Cells; 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 cewll manufacturing. 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-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.
Experimental: Dose Level +2; EGFR+ T Cell Dose (Day 0) 50 x 10^6 cells	Biological: CMV/HIV-CAR T Cells; 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 cewll manufacturing. 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-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities (DLT)	Toxicity will be graded per CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria on CRS/Neurotoxicity: DLT.	Up to 28 days after the infusion
Toxicity profile	Toxicity will be graded per CTCAE v5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Criteria on CRS/Neurotoxicity: all other toxicities to define the toxicity profile.	Up to 28 days after the infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4+ T cell count and HIV RNA levels	CD4+ T cell count and HIV RNA levels in the peripheral blood;	Up to 28 days after the infusion
EGFR+ CD3+ T cells	Number, percentage and persistence of EGFR+ CD3+ T cells in the peripheral blood and EGFR- CD3+ T cells in peripheral blood	Up to 28 days after the infusion
Cytokine levels	Cytokine levels in the peripheral blood post CAR T cell infusion.	Up to 28 days after the infusion
Number of CMV/HIV-CAR T cells	Number of CMV/HIV-CAR T cells: measured by qPCR in peripheral blood); and Using two in-depth interviews (1) shortly following screening (within 2 weeks), and 2) within 1 month of initiating Step 4, we will assess perceptions of the CMV/HIV-CAR T cell intervention and overall trial experiences in participants	Up to 28 days after the infusion

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Investigators: Principal Investigator: John H. Baird, MD, City of Hope Medical Center; Principal Investigator: David (Davey) Smith, MD, UCSD, San Diego Center for AIDS Research

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): December 11, 2026

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: HIV-1, PLWH (Healthy People Living with HIV-1) autologus; CMV-specific T cells, anti-retroviral therapy (ART), Immunotherapy
• Other Study ID Numbers: 22508

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No