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

NCT ID: NCT06252402

Last Updated: 2025-02-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-19
• Study Completion Date: 2026-12-11

Brief 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.

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.

Conditions

HIV-1

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Level -1

EGFR+ T Cell Dose (Day 0) 5 x 10\^6 cells

Group Type: EXPERIMENTAL

CMV/HIV-CAR T Cells

Intervention Type: BIOLOGICAL

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.

Dose Level +1

EGFR+ T Cell Dose (Day 0) 25 x 10\^6 cells

Group Type: EXPERIMENTAL

CMV/HIV-CAR T Cells

Intervention Type: BIOLOGICAL

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.

Dose Level +2

EGFR+ T Cell Dose (Day 0) 50 x 10\^6 cells

Group Type: EXPERIMENTAL

CMV/HIV-CAR T Cells

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John H. Baird, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

David (Davey) Smith, MD

Role: PRINCIPAL_INVESTIGATOR

UCSD, San Diego Center for AIDS Research

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

UCSD, Division of Infectious Diseases and Global Public Health

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marvin Hanashiro

Role: CONTACT

mhanashiro@health.ucsd.edu

(619) 543-3740

Steven Hendrickx

Role: CONTACT

smhendrickx@health.ucsd.edu

(619) 543-6968

Facility Contacts

David Smith, MD

Role: primary

Other Identifiers

22508

Identifier Type: -

Identifier Source: org_study_id