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

Status: Recruiting
Location: See all (2) locations...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Early Phase 1
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
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: t
View:

• 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.

Locations
United States
California
City of Hope Medical Center
RECRUITING
Duarte
UCSD, Division of Infectious Diseases and Global Public Health
RECRUITING
San Diego
Contact Information
Primary
Marvin Hanashiro
mhanashiro@health.ucsd.edu
(619) 543-3740
Backup
Steven Hendrickx
smhendrickx@health.ucsd.edu
(619) 543-6968
Time Frame
Start Date: 2024-12-19
Estimated Completion Date: 2026-12-11
Participants
Target number of participants: 15
Treatments
Experimental: Dose Level -1
EGFR+ T Cell Dose (Day 0) 5 x 10\^6 cells
Experimental: Dose Level +1
EGFR+ T Cell Dose (Day 0) 25 x 10\^6 cells
Experimental: Dose Level +2
EGFR+ T Cell Dose (Day 0) 50 x 10\^6 cells
Related Therapeutic Areas
Sponsors
Leads: City of Hope Medical Center

This content was sourced from clinicaltrials.gov