CAR T Cells for HIV

Recruiting at 1 trial location

Overseen By Steven Hendrickx

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: City of Hope Medical Center

Must be taking: Antiretrovirals

Disqualifiers: Concurrent illness, Antiretroviral resistance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 1 day

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover a new treatment for HIV-1 using specially engineered immune cells called CAR T cells (CMV/HIV-CAR T Cells). These cells are designed to locate and destroy HIV-infected cells, potentially leading to long-term remission for those already on anti-retroviral therapy (ART). The trial will test different doses of these engineered cells to evaluate their effectiveness. Individuals living with HIV-1, currently on stable ART with undetectable virus levels, and with a CD4+ cell count of at least 450 may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires participants to interrupt their ART regimen for 4 days before a procedure called leukapheresis (a process to collect blood cells). Other current medications are not specified in the protocol.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CMV/HIV-CAR T cells, a new treatment under study for HIV, have shown promise in early research. These studies suggest that the treatment might naturally resist HIV infection because the modified T cells are mostly CD8+ cells, which fight infections.

Since this trial is in its early stages, information on treatment tolerance remains limited. Early trials like this one usually focus on assessing safety. Researchers closely monitor for side effects or problems to ensure participants' safety. The aim is to find the safest dose and identify any serious reactions.

In summary, while early findings are hopeful, the safety of CMV/HIV-CAR T cells in humans is still under careful evaluation. Participants in these trials play a key role in discovering new treatments that could potentially improve the lives of many people living with HIV. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CMV/HIV-CAR T Cells for HIV treatment because they represent a novel approach, using the body's own immune system to fight the virus. Unlike standard antiretroviral therapies that aim to suppress HIV replication, CAR T Cells are engineered to specifically target and destroy HIV-infected cells. This method has the potential to provide a more targeted and long-lasting response against HIV. Additionally, the use of varying doses of engineered T cells in the trial aims to optimize safety and effectiveness, potentially leading to a breakthrough in achieving sustained remission without continuous medication.

What evidence suggests that CMV/HIV-CAR T Cells might be an effective treatment for HIV?

Research has shown that CMV/HIV-CAR T cells could offer a promising treatment for HIV. One study using a specialized mouse model for HIV demonstrated that a CMV vaccine administered during ART (antiretroviral therapy) increased the number of these CAR T cells in the blood. This finding suggests that the treatment might help the body combat HIV by keeping these specialized T cells active for longer. In this trial, participants will receive varying doses of CMV/HIV-CAR T cells to assess their effectiveness. CAR T cells are engineered to locate and destroy HIV-infected cells. By also targeting CMV, the treatment aims to extend the lifespan and enhance the function of these T cells. Early results indicate this approach might improve HIV management, though further research is necessary to confirm its effectiveness in humans. ^{1 2 3 4 6}

Who Is on the Research Team?

John Baird, M.D.

Principal Investigator

City of Hope Medical Center

David (Davey) Smith, MD

Principal Investigator

UCSD, San Diego Center for AIDS Research

Are You a Good Fit for This Trial?

This trial is for people living with HIV who are on anti-retroviral therapy (ART) but still have the virus in their bodies. Participants should be generally healthy and have a history of cytomegalovirus (CMV), which most HIV-positive individuals do.

Inclusion Criteria

My HIV is under control with ART and undetectable for over 48 weeks.

Documented HIV-1 infection anytime prior to study entry

CD4+ cell count ≥ 450 cells/μL

Exclusion Criteria

Concurrent illness or comorbid condition

I have HIV that hasn't responded to at least two types of treatments.

I have previously received experimental HIV treatment or gene therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis and ART Interruption

Participants temporarily interrupt 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. ART is resumed immediately after leukapheresis.

1 week

1 visit (in-person)

Treatment

Participants receive a single intravenous infusion of autologous CMV/HIV-CAR T cells. Up to three doses may be explored.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including dose limiting toxicities and cytokine levels.

4 weeks

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• CMV/HIV-CAR T Cells

Trial Overview The study is testing CMV/HIV-CAR T Cells, a type of immunotherapy designed to target and destroy HIV-infected cells using the body's own modified T cells that can also respond to CMV, potentially leading to long-term remission of HIV.

How Is the Trial Designed?

Group I: Dose Level -1 Experimental Treatment 1 Intervention

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

Group II: Dose Level +2 Experimental Treatment 1 Intervention

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

Group III: Dose Level +1 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Published Research Related to This Trial

Engineering T cells to express HIV-specific chimeric antigen receptors (CARs) combined with a cytomegalovirus (CMV) vaccine can enhance T cell activation and persistence, particularly during low HIV antigen levels seen in antiretroviral therapy (ART).

In a humanized HIV mouse model, CMV vaccination during ART led to increased expansion of CMV-HIV CAR T cells, which correlated with better control of HIV viral load and reduced presence of HIV-infected cells in the bone marrow, suggesting a promising strategy for HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical data supporting immunotherapy for HIV using CMV-HIV-specific CAR T cells with CMV vaccine. Guan, M., Lim, L., Holguin, L., et al.[2023]

The study developed a novel CAR-T therapy using duoCARs that target multiple conserved sites on the HIV-1 envelope, showing a remarkable ability to reduce HIV infection by up to 99% in vitro and over 97% in vivo.

Transduced T cells demonstrated long-term control of HIV infection and protection against diverse HIV-1 strains, suggesting that this approach could effectively treat HIV-1 in patients and prevent the loss of crucial CD4+ T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model. Anthony-Gonda, K., Bardhi, A., Ray, A., et al.[2020]

Adoptive cellular therapies targeting CMV-specific T cells show promise as a non-toxic alternative to traditional antiviral treatments for patients undergoing allogeneic hematopoietic stem cell transplantation, with preliminary results indicating low risk of graft-versus-host disease.

Recent advancements in generating CMV-specific T cells, particularly targeting the pp65 antigen, suggest that these therapies can effectively restore anti-CMV immunity, demonstrating antiviral activity after infusion in early clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials with CMV-specific T cells. Peggs, KS., Mackinnon, S.[2018]

Anti-HIV duoCAR T cell therapy has shown promising efficacy in eliminating HIV-infected cells in humanized mice, indicating its potential to target and destroy reactivated HIV-infected cells in people with HIV.

The therapy effectively localizes to lymphoid tissues and demonstrates the ability to kill HIV-infected CD4+ T cells and monocytes/macrophages, supporting its safety and efficacy as it moves into clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo killing of primary HIV-infected cells by peripheral-injected early memory-enriched anti-HIV duoCAR T cells. Anthony-Gonda, K., Ray, A., Su, H., et al.[2023]

Cellular responses from CD8 and CD4 lymphocytes are effective against CMV infections but ineffective against HIV, highlighting the need for different therapeutic approaches for these viruses.

Monitoring and characterizing specific T-cell responses can aid in assessing immune status and developing targeted therapies or vaccines, as well as providing a quantitative measure of the immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro selection of HIV and CMV specific T-lymphocytes. Li Pira, G., Bottone, L., Ivaldi, F., et al.[2006]

A novel method using synthetic CpG oligodeoxynucleotides and modified vaccinia Ankara (MVA) to expand CMV-specific CD4(+) and CD8(+) T cells resulted in a 30-fold increase in T cell populations within 10 days, demonstrating high efficacy for potential therapeutic use.

The expanded T cells showed minimal alloreactivity and strong cytotoxic activity against CMV, making this approach promising for managing CMV viremia in patients undergoing hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro expansion of polyclonal T-cell subsets for adoptive immunotherapy by recombinant modified vaccinia Ankara. La Rosa, C., Wang, Z., Lacey, SF., et al.[2008]

Dual-CAR T cells, which express both 4-1BB/CD3-ζ and CD28/CD3-ζ endodomains, showed superior expansion and effectiveness in preventing CD4+ T cell loss in HIV-infected humanized mice compared to traditional CAR T cells.

When protected from HIV infection, Dual-CAR T cells significantly reduced viral levels and improved HIV suppression during antiretroviral therapy, highlighting their potential as a powerful treatment strategy for HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo. Maldini, CR., Claiborne, DT., Okawa, K., et al.[2023]

In a study of 23 AIDS patients with cytomegalovirus (CMV) infection, common symptoms included fever, cough, and retinitis, with a significant decrease in CD4+ T cell counts compared to non-CMV patients, indicating a severe immune compromise.

Routine screening for CMV infection using pp65 antigen and specific anti-CMV IgM is recommended for AIDS patients with CD4+ T cell counts of 100 cells/µL or less, especially when they present with symptoms like fever and blurred vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Twenty-three cases of cytomegalovirus infection in acquired immunodeficiency syndrome]. Tao, MM., Ye, JJ., Kuang, JQ.[2014]

Anti-HIV chimeric antigen receptor (CAR) T cells have the potential to provide a cure for HIV by specifically targeting and eliminating virus-producing cells, even in patients undergoing successful antiretroviral therapy.

The review highlights advancements in CAR design aimed at improving their effectiveness and targeting precision, while also addressing ongoing challenges that must be overcome to make this treatment a viable option for curing HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status and future development of anti-HIV chimeric antigen receptor T-cell therapy. Mao, Y., Zhao, C., Zheng, P., et al.[2022]

Anti-CD3 activated T cells (ATCs) armed with a bispecific antibody targeting CMV (CMVBi) demonstrated significant cytotoxicity against CMV-infected cells, achieving up to 82% specific killing at certain effector-to-target ratios, compared to less than 20% for unarmed ATCs.

This innovative approach, which does not rely on major histocompatibility complex (MHC) restrictions, shows promise for preventing or treating CMV infections in patients undergoing allogeneic stem cell or organ transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting cytomegalovirus-infected cells using T cells armed with anti-CD3 × anti-CMV bispecific antibody. Lum, LG., Ramesh, M., Thakur, A., et al.[2021]

In a study involving 16 patients, treatment with polyclonal CMV-specific T-cell lines led to significant in-vivo expansion of these immune cells, effectively reconstituting viral immunity against CMV infection after transplantation.

The use of these T-cell lines was shown to be effective, as eight patients did not require antiviral drugs, and only two experienced subsequent reactivation of the virus, highlighting the potential of this therapy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Peggs, KS., Verfuerth, S., Pizzey, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9062763/

Pre-clinical data supporting immunotherapy for HIV using ... Using a humanized HIV mouse model, we show that CMV vaccination during ART accelerates CMV-HIV CAR T cell expansion in the peripheral blood and that higher ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12090794/

Persistence of CMV-specific anti-HIV CAR T cells after ... These data suggest that CAR Tc will require additional interventions to cure HIV infection. KEYWORDS: adoptive immunotherapy, CD4-CAR T cells, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06252402

Study Details | NCT06252402 | CMV-specific HIV-CAR T ... 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 ...

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06252402

CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/ ... We propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo.

5. cirm.ca.gov cirm.ca.gov/our-progress/awards/evaluation-safety-and-feasibility-cytomegalovirus-specific-anti-hiv-chimeric-antigen-receptor-cmv-hiv-car-t-cells-people-hiv/

Evaluation of Safety and Feasibility of Cytomegalovirus ... We propose to treat them with CAR T cells which will attack and eliminate HIV-infected cells. These cells will also be able to recognize and be activated by ...

6. journals.asm.org journals.asm.org/doi/10.1128/jvi.01933-24

Persistence of CMV-specific anti-HIV CAR T cells after ... These studies aim to genetically modify CMV-specific Tc with HIV-CAR2 vectors and link HIV immunotherapy to persistent CMV antigen stimulation.