Modified T Cells for HIV Therapy

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Overseen BySu Kyung Kim, PhD, CRNP, WHNP-BC
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: University of Pennsylvania
Must be taking: HAART
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat HIV by using participants' own T cells, a type of white blood cell, to better target the virus. The goal is to determine if these modified T cells, specifically CD4 CAR+CCR5 ZFN T-cells, are safe and can effectively reduce HIV infection. Participants will receive the modified cells and then pause their regular HIV treatment for a period to test the results. This trial may suit individuals who have been stable on HIV medication with a low viral load and are open to trying a new treatment method. As a Phase 1 trial, the research focuses on understanding how the treatment works 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 does not specify if you need to stop all current medications, but you cannot be taking a non-nucleoside reverse transcriptase inhibitor (NNRTI) or certain medications affecting blood clotting before the procedure. It's best to discuss your specific medications with the study team.

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

Research has shown that a new HIV treatment involving modified T-cells has generally been safe in earlier studies. These studies involved altering a person's own T-cells (a type of white blood cell) to combat HIV. For instance, one study found that these modified T-cells were well-tolerated, with participants experiencing no serious side effects. Another study confirmed the safety of using these gene-edited T-cells, as they did not cause major issues. These findings suggest the treatment is likely safe for participants, though it remains in the early stages of testing.12345

Why do researchers think this study treatment might be promising?

Most treatments for HIV work by suppressing the virus with daily antiretroviral medications. But the investigational therapy using CD4 CAR+CCR5 ZFN T-cells is different, as it aims to modify the body's own immune cells to resist HIV infection. This approach involves reprogramming T-cells to directly target and eliminate HIV-infected cells, offering a potential one-time intervention that could reduce or eliminate the need for lifelong medication. Researchers are excited because this method not only targets the virus more precisely but also represents a novel approach that could lead to long-term remission or even a functional cure.

What evidence suggests that CD4 CAR+CCR5 ZFN T-cells might be an effective treatment for HIV?

Research shows that a new type of modified T-cells, known as CD4 CAR+CCR5 ZFN T-cells, could help treat HIV. These T-cells have been altered to enhance the body's ability to combat the virus. In earlier studies, these modified T-cells resisted HIV infection, both in the lab and in early human trials. Approximately 8.8% of these T-cells were successfully modified, suggesting they might help reduce the virus in the body. Although these results are preliminary, they offer hope for improved HIV treatment in the future. Participants in this trial will receive these modified T-cells, with Cohort 1 beginning treatment interruption about 24 hours after receiving the T-cells, and Cohort 2 beginning treatment interruption about 8 weeks later.12346

Who Is on the Research Team?

Pablo Tebas, MD profile | PennMedicine.org

Pablo Tebas, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV who've had a stable viral load (≤50 copies/mL) for at least 24 weeks, are on their first or second antiretroviral therapy, and have certain levels of T cells. They must not have hepatitis B/C, AIDS, cancer history (except some skin cancers), heart disease without approval, bleeding disorders, recent gene therapy or experimental vaccines for HIV.

Inclusion Criteria

I am infected with HIV-1.
Negative HBsAg (hepatitis B) within 6 months prior to enrollment
Have a recorded viral load set point prior to starting antiretroviral therapy
See 10 more

Exclusion Criteria

I have a condition that causes unusual bleeding.
I don't have active or unstable heart problems, or if I do, my doctor approves my participation.
Breast-feeding, pregnant, or unwilling to use acceptable methods of birth control
See 11 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Subjects receive a single infusion of CD4 CAR+CCR5 ZFN modified T cells

1 day for Cohort 1, 8 weeks for Cohort 2
1 visit (in-person)

Analytical Treatment Interruption (ATI)

Participants undergo a 16-week ATI, with monitoring of viral load and CD4 count

Up to 16 weeks
Regular monitoring visits

Extension of ATI

Participants with viral loads ≤1000 copies/ml continue ATI until specific criteria are met

Variable

Reinitiation of Antiretroviral Therapy

Participants restart antiretroviral therapy with monthly visits until HIV RNA is below quantification limit

Variable
Monthly visits

Secondary Follow-up

All subjects are followed for safety for up to 5 years post-infusion

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

  • CD4 CAR+CCR5 ZFN T-cells
Trial Overview The study tests modified T-cells designed to fight HIV. Participants' own T-cells will be taken and genetically altered using CD4 CAR+CCR5 ZFN technology to target the virus. The goal is to assess safety and impact on the infection.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Cohort 2Experimental Treatment1 Intervention
Group II: Cohort 1Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials
2,118
Recruited
45,270,000+

Published Research Related to This Trial

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

Citations

CCR5-edited CD4+ T cells augment HIV-specific immunity to ...We conducted a phase I clinical trial that infused CCR5 gene–edited CD4 + T cells to determine how these T cells can better enable HIV cure strategies.
Gene Editing of CCR5 in Autologous CD4 T Cells ...The median concentration of CCR5-modified CD4 T cells at 1 week was 250 cells per cubic millimeter. This constituted 8.8% of circulating ...
CCR5 gene editing and HIV immunotherapy - PubMed CentralThis study focuses on the pivotal role of CC chemokine receptor 5 (CCR5) gene editing in HIV immunotherapy, particularly highlighting the natural resistance to ...
NCT03617198 | CD4 CAR+ ZFN-modified T Cells in HIV ...This research study is being carried out to study a new way to possibly treat HIV. As part of this study, doctors will take some of your own white blood cells, ...
CCR5 Gene Editing of Resting CD4+ T Cells by Transient ...Both activated and resting primary CD4+ T cells transduced with CCR5-ZFNs NILV showed resistance to HIV-1 infection in vitro. Furthermore, NILV transduced ...
52. Increases in CD4 Counts and Effects on HIV ...We report data relating to safety, increases in CD4 T-cell counts, persistence and trafficking of SB-728-T, and effects on HIV-RNA (VL) and proviral DNA from ...
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