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