Donor-Derived T-cell Therapy for HIV

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

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a multi-site phase 1 study of the safety, immunologic and virologic responses of ex vivo expanded donor-derived (DD) HIV-1 multi-antigen specific T-cell (HST) with non-escaped epitope targeting (NEET) therapy as a therapeutic strategy in HIV-infected individuals following Allogeneic Bone Marrow Transplantation (alloBMT).

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.

Is donor-derived T-cell therapy for HIV safe for humans?

Donor-derived virus-specific T cells have shown similar safety profiles in managing viral infections after stem cell transplantation in children and young adults, suggesting they are generally safe for human use. ^{1 2 3 4 5}

How is the Donor-Derived T-cell Therapy for HIV different from other treatments?

This treatment is unique because it uses donor-derived T-cells specifically designed to target multiple parts of the HIV virus, potentially preventing the virus from rebounding after stem cell transplants. Unlike traditional treatments that rely on antiretroviral drugs, this therapy aims to provide long-lasting HIV-specific immunity by eliminating newly infected cells before they can spread. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Donor-Derived T-cell Therapy for HIV?

Research shows that donor-derived virus-specific T cells (VSTs) can effectively restore virus-specific immunity and control viral infections after stem cell transplants, with response rates of 60% to 90% in recipients. Additionally, HIV-specific T cells generated from naive T cells have been shown to suppress active HIV in laboratory settings, suggesting potential for this treatment in managing HIV. ^{4 7 8 9 10}

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

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]

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) 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Identification of the best-suited donor for generating virus-specific T cells. [2020]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

HIV-Specific T Cells Generated from Naive T Cells Suppress HIV In Vitro and Recognize Wide Epitope Breadths. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

T cells for viral infections after allogeneic hematopoietic stem cell transplant. [2021]

6. United States 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. [2023]

7. United States 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

HIV-Specific T Cells Can Be Generated against Non-escaped T Cell Epitopes with a GMP-Compliant Manufacturing Platform. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals. [2022]

10. United States 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. [2022]