Donor-Derived T-cell Therapy for HIV

Not currently recruiting at 1 trial location

Overseen By Richard Ambinder, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressive antibodies

Disqualifiers: Uncontrolled infections, Active GVHD, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effects of a new therapy using special T-cells from donors to help fight HIV in people who have had a bone marrow transplant. The treatment, known as DD HST-NEETs (Donor-Derived HIV-Specific T-cells), boosts the body’s immune system with these donor-derived T-cells, potentially offering a new way to manage HIV. People living with HIV who are on effective antiretroviral therapy and have undergone a bone marrow transplant for blood cancers might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity 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 taking your current medications, but you must continue your antiretroviral therapy throughout the study.

What prior data suggests that this T-cell therapy is safe for humans?

Research has shown that treatments using special immune cells from donors, such as DD HST-NEETs, appear safe. In one study, researchers monitored six people for safety, and none experienced serious side effects from the treatment. This suggests that the treatment is generally well-tolerated by recipients. Although this is early research, the absence of serious negative effects in these participants is a positive indicator of the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Donor-Derived HIV-Specific T-cells (DD HST-NEETs) because they offer a novel approach to tackling HIV by using the body's own immune system. Unlike standard antiretroviral therapies that suppress the virus, DD HST-NEETs are designed to enhance the immune response specifically against HIV. This treatment involves using T-cells derived from donors, which are engineered to target and combat HIV-infected cells. This method not only aims to control the virus more effectively but also potentially reduces the reliance on lifelong medication regimens.

What evidence suggests that DD HST-NEETs might be an effective treatment for HIV?

Research shows that special immune cells from donors, called donor-derived HIV-specific T-cells (DD HST-NEETs), can help the body fight HIV. These T-cells target the virus more effectively. Studies have found that this therapy can help the immune system recognize and control the virus. Early results suggest that this treatment is generally safe and doesn't cause serious side effects. The success of similar therapies offers hope that DD HST-NEETs, which participants in this trial will receive, might effectively manage HIV. ^{1 5 6 7 8}

Who Is on the Research Team?

Richard Ambinder, MD, PhD

Principal Investigator

Johns Hopkins University

Michael Keller, MD

Principal Investigator

CNMC

Are You a Good Fit for This Trial?

This trial is for HIV-infected adults who've had an allogeneic bone marrow transplant. They must be on effective antiretroviral therapy, have good organ function, no active hepatitis C or B, and a Karnofsky score of ≥ 70. Pregnant women can't participate, and participants need to agree to study requirements.

Inclusion Criteria

Serum creatinine ≤ 2x upper limit normal.

No active HCV infection. (If seropositive, participant must have no measureable HCV RNA within 30 days of enrollment).

My organs are healthy enough for a bone marrow transplant.

Exclusion Criteria

Donor Exclusion Criteria for Procurement for DD HST-NEETs Manufacturing:

You are not eligible to participate if you have a condition called DD HST-NEETs and require infusion treatment.

Donor exclusion criteria will be followed as per institution standard operating procedures (SOPs).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DD HST-NEETs at a dose of 2x107/m2 within 30 days of screening visit

30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

45 days

Long-term follow-up

Participants are monitored for long-term safety and virologic responses

3 years

What Are the Treatments Tested in This Trial?

Interventions

• DD HST-NEETs

Trial Overview The trial tests donor-derived HIV-specific T-cells (DD HST-NEETs) in patients post-bone marrow transplant to see if they're safe and how they affect the immune system and HIV itself. It's a phase 1 study conducted across multiple sites.

How Is the Trial Designed?

Group I: Donor Derived HIV-Specific T-cells (DD HST-NEETs) Experimental Treatment 1 Intervention

Participants who meet specified inclusion criteria including neutrophil recovery post-transplant and for whom donor products have passed release testing will receive DD HST-NEETs at a dose of 2x107/m2 within 30 days of screening visit.

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+

Published Research Related to This Trial

The study presents a novel approach to generating multi-antigen HIV-specific T cells from HLA-A02+ donors, which could enhance the effectiveness of adoptive T cell therapy in preventing HIV rebound after hematopoietic stem cell transplant (HSCT).

These engineered T cells demonstrated the ability to target and suppress active HIV in vitro, indicating potential for broader immune responses compared to previous therapies that were limited by single-epitope specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths. Patel, S., Chorvinsky, E., Albihani, S., et al.[2021]

A 12-year-old patient with HIV underwent umbilical cord blood transplantation from a CCR5∆32 homozygous donor, which led to the absence of detectable HIV DNA in peripheral blood post-transplant, suggesting a potential cure.

Despite the successful transplantation and conditioning, HIV DNA was still found in various tissues 73 days later, indicating that HIV reservoirs may persist in the body even after treatment, emphasizing the need for thorough tissue analysis in HIV cure research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of CCR5∆32 Homozygous Umbilical Cord Blood in a Child With Acute Lymphoblastic Leukemia and Perinatally Acquired HIV Infection. Rothenberger, M., Wagner, JE., Haase, A., et al.[2022]

HIV-specific T cells (HSTs) targeting conserved, non-escaped HIV epitopes have been successfully manufactured and expanded, showing the ability to kill reactivated HIV-infected cells and produce a strong immune response.

These HST-NEETs could potentially be used in combination with latency reversing agents (LRAs) to eliminate HIV from latently infected reservoirs in patients, offering a promising strategy for HIV eradication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-Specific T Cells Can Be Generated against Non-escaped T Cell Epitopes with a GMP-Compliant Manufacturing Platform. Patel, S., Hanajiri, R., Grant, M., et al.[2021]

Adoptive transfer of donor-derived virus-specific T cells (VSTs) has shown effectiveness in restoring immunity against viral infections after hematopoietic stem cell transplantation (HSCT), with success rates of 70% to 90% in recipients.

Recent studies have also demonstrated that using closely matched third-party VSTs can provide protection, achieving response rates of 60% to 70%, which is crucial for patients with virus-naïve donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells for viral infections after allogeneic hematopoietic stem cell transplant. Bollard, CM., Heslop, HE.[2021]

The study successfully generated engineered human invariant natural killer T (iNKT) cells that can help reduce graft-versus-host disease (GvHD) while still allowing for the beneficial graft-versus-leukemia (GvL) effect, making them a promising option for patients undergoing allo-HSCT.

These engineered 3rdHSC-iNKT cells demonstrated strong anti-GvHD activity by targeting and eliminating antigen-presenting myeloid cells in laboratory models, without hindering the ability of allogeneic T cells to fight tumors, indicating their potential as an effective prophylactic treatment for GvHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers. Li, YR., Zeng, S., Dunn, ZS., et al.[2022]

Allogeneic hematopoietic stem cell transplantation (HSCT) has been used for decades to treat various malignancies, and there is growing interest in its potential for HIV-1-infected patients, especially as their risk for cancer increases due to improved life expectancy from antiretroviral therapy.

The review analyzes over 25 years of data on HSCT in HIV-1 patients, suggesting that while previous attempts to use HSCT for HIV treatment were largely unsuccessful, there may be new strategies to effectively target the HIV-1 reservoir in conjunction with HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation in patients with human immunodeficiency virus: the experiences of more than 25 years. Hütter, G., Zaia, JA.[2021]

All three patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) remained in remission for 4-6 years, showing significant reductions in HIV reservoir measurements, indicating potential long-term benefits of HSCT in HIV treatment.

However, one patient experienced a viral rebound 4 years post-transplant, suggesting that replication-competent HIV can re-emerge even after substantial changes to the HIV reservoir and immune response, highlighting the need for ongoing monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals. Koelsch, KK., Rasmussen, TA., Hey-Nguyen, WJ., et al.[2022]

In a study of 145 pediatric and young adult patients who received virus-specific T cells (VSTs) after hematopoietic stem cell transplantation, there was no significant difference in clinical response rates between donor-derived (DD) VSTs and third-party (TP) VSTs, with response rates of 65.6% and 62.7% respectively.

Both DD and TP VSTs demonstrated similar safety profiles and effectiveness in managing viral infections, suggesting that TP VSTs can be a viable and more accessible alternative to DD VSTs for controlling infections post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third-Party and Patient-Specific Donor-Derived Virus-Specific T Cells Demonstrate Similar Efficacy and Safety for Management of Viral Infections after Hematopoietic Stem Cell Transplantation in Children and Young Adults. Galletta, TJ., Lane, A., Lutzko, C., et al.[2023]

In a study involving 28 patients and 32 virus-specific T cell (VST) treatments over 3 years, the average yield of viable VSTs was 1.83 million cells, with a mean purity of 62.9%, indicating a robust method for generating these cells for antiviral therapy.

The research found that the frequency of VSTs in the donor's blood, particularly for cytomegalovirus (CMV), strongly predicts the quantity of VSTs in the final product, emphasizing the importance of careful donor selection in optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of the best-suited donor for generating virus-specific T cells. Tasnády, S., Karászi, É., Szederjesi, A., et al.[2020]

Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to a significant reduction in detectable HIV-1 in blood and gut tissue, resulting in temporary periods of HIV-1 remission without antiretroviral therapy in two patients.

Despite the initial success, both patients experienced a rebound of the virus within two weeks after stopping treatment, indicating that long-lived HIV-1 reservoirs may still exist and contribute to viral persistence, highlighting the need for further research on these reservoirs to achieve lasting remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Henrich, TJ., Hanhauser, E., Marty, FM., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04248192

Study Details | NCT04248192 | Evaluate the Safety, ... Evaluate the Safety, Immunologic, and Virologic Responses of Donor Derived (DD) HIV-Specific T-cells (HST) in HIV-infected Individuals Following Allogeneic ...

2. nature.com nature.com/articles/s41467-025-59810-2

Autologous HIV-specific T cell therapy targeting conserved ... We report that two infusions of autologous HST-NEETs in six adults with HIV on ART is well-tolerated following >45 weeks of safety monitoring post infusions.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6838524/

HIV-Specific T Cells Can Be Generated against Non ... The ICS plots show representative data from two HIV-negative donor-derived HST-NEETneg cell products (F). p values represent significance of ...

4. withpower.com withpower.com/trial/phase-1-4-2020-ec98d

Donor-Derived T-cell Therapy for HIV · Info for Participants Research shows that donor-derived virus-specific T cells (VSTs) can effectively restore virus-specific immunity and control viral infections after stem cell ...

5. cancer.gov cancer.gov/clinicaltrials/NCI-2021-01722

HIV-Specific T-Cell Therapy (DD HST-NEETs) for ... This phase I trial investigates the safety, immune and virus responses of human immunodeficiency virus (HIV)-specific T-cell therapy (donor derived ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12081906/

Autologous HIV-specific T cell therapy targeting conserved ... Novel cellular therapies may enable HIV control or cure. HIV-specific T cells targeting conserved immunogenic protein regions of HIV Gag/Pol and ...

7. synapse.patsnap.com synapse.patsnap.com/drug/6a4c583b8b57483d801b68809faaf15e

Donor Derived HIV-Specific T-cells (DD HST-NEETs)(Children's ... Six participants completed safety monitoring. No serious product-related toxicities are observed. Secondary endpoints are to assess expansion and persistence of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03485963

NCT03485963 | HIV-1 Specific T -Cells (HST-NEETs) for ... The primary objective of this study is to evaluate the safety and tolerability of expanded HIV-specific T cell therapy (HST-NEETs) in HIV-infected individuals ...