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

ConditionHIV-1

Trial statusRecruiting

Trial phaseEarly Phase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorCity of Hope Medical Center

About this trial

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

This trial accepts healthy volunteers

Qualifiers

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);

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

CMV/HIV-CAR T Cells
Biological/Vaccine
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.

Treatment groups

15 Participants

are divided into 3 treatment groups

Group A: Dose Level -1Experimental treatment 1 intervention

Group B: Dose Level +1Experimental treatment 1 intervention

Group C: Dose Level +2Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame