DCreg Cell Therapy for Liver Transplant Recipients

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Angus W. Thomson PhD DSc

Must be taking: Immunosuppressants

Disqualifiers: Severe heart or lung disease, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called donor-derived DCreg, a type of cell therapy, for individuals who have received a liver transplant from a living donor. The goal is to determine if this treatment can safely help recipients reduce or stop their use of immunosuppressive drugs, which are typically needed to prevent organ rejection. Participants who had their first liver transplant 1 to 3 years ago and have stable liver health might be suitable candidates. The trial involves receiving an infusion of DCreg cells and then gradually reducing immunosuppressive medication under close monitoring. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

Participants will remain on their current standard immunosuppression medications initially, but will begin to slowly reduce these medications one week after receiving the DCreg infusion.

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

Research has shown that a new treatment using donor-derived regulatory dendritic cells (DCreg) looks promising. These treatments have been tested in liver transplant recipients. Results so far suggest that DCreg infusions are generally safe and well-tolerated, with no major side effects directly linked to the treatment.

One study examined the effects of DCreg on the immune system and found that the treatment might reduce the need for standard immunosuppressive drugs, which can have serious side effects.

Although researchers are still studying the treatment, the absence of major negative side effects in early trials is a positive sign for its safety. It is important to note that since this trial is in the early stages, it primarily focuses on ensuring the treatment's safety for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for liver transplant recipients involve long-term immunosuppressive drugs to prevent organ rejection. But DCreg Cell Therapy is different because it uses donor-derived regulatory dendritic cells to potentially reduce the need for these medications. These cells are infused into the recipient and may help the body accept the new liver more naturally. Researchers are excited because this approach could minimize the side effects associated with long-term immunosuppression, improving the quality of life for transplant patients.

What evidence suggests that donor-derived DCreg might be an effective treatment for liver transplant recipients?

Research has shown that special cells from the liver donor, called donor-derived regulatory dendritic cells (DCreg), might help liver transplant patients reduce their use of standard immunosuppressive drugs. These cells may help the body accept the new liver without attacking it. In this trial, participants will receive an infusion of DCreg one week before starting immunosuppression weaning. One study found that infusing these cells was safe and did not cause significant side effects. Early animal studies demonstrated that these cells could help the transplanted liver last longer. While research in humans continues, initial findings are promising for reducing the need for long-term medication. ^{4 5 6 7 8}

Who Is on the Research Team?

Abhinav Humar

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for low-risk liver transplant recipients who are 1-3 years post-transplant without recent rejection or significant fibrosis. They must have stable liver function and no severe other diseases. Donors must be healthy, able to consent, and free from certain infections like HIV or hepatitis.

Inclusion Criteria

Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(a)

I haven't received any live vaccines in the last 12 weeks.

Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(a) (does not preclude donors from undergoing leukapheresis but cells may not be infused into recipient)

Exclusion Criteria

I have or had Hepatitis B or C, but it's not currently active.

Prior other solid organ transplant

Positive antigen-antibody immunoassay for HIV-1/2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

DCreg Infusion

Participants receive a single infusion of donor-derived regulatory dendritic cells (DCreg) one week prior to the initiation of immunosuppression weaning

1 week

1 visit (in-person)

Immunosuppression Weaning

Participants are slowly weaned off immunosuppression following the DCreg infusion

Varies per participant

Follow-up

Participants are monitored for safety and effectiveness after immunosuppression withdrawal, including liver biopsies at 1 year and 3 years post-withdrawal

3 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Donor-derived DCreg

Trial Overview The study tests a single infusion of donor-derived DCreg cells in patients after living donor liver transplantation. It aims to see if these cells can allow safe reduction of immunosuppression drugs over time with follow-up biopsies at one and three years post-weaning.

How Is the Trial Designed?

Group I: DCreg Prior to Weaning Experimental Treatment 1 Intervention

Regulatory dendritic cells that were derived from the recipient's liver donor will be infused into the recipient one week prior to the initiation of immunosuppression weaning.

Who Is Running the Clinical Trial?

Angus W. Thomson PhD DSc

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

Regulatory dendritic cells (DCregs) were successfully manufactured in large quantities under Good Manufacturing Practice conditions, achieving a high viability rate of 94% and meeting quality criteria for infusion into 28 liver transplant recipients.

The process resulted in a conversion rate of 28% from monocytes to DCregs, with 92.6% of the products achieving the target cell range for infusion, indicating a promising approach to enhance antigen-specific tolerance in organ transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacturing and validation of Good Manufacturing Practice-compliant regulatory dendritic cells for infusion into organ transplant recipients. Zahorchak, AF., DeRiggi, ML., Muzzio, JL., et al.[2023]

Current immunosuppressive regimens for organ transplants have significant side effects, including increased risk of infections and cancers, highlighting the need for safer alternatives.

Regulatory dendritic cell therapy shows promise in promoting transplant tolerance and may allow for the reduction or complete withdrawal of immunosuppressive drugs, with early clinical trials currently assessing its efficacy in organ transplantation and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory dendritic cells for human organ transplantation. Thomson, AW., Metes, DM., Ezzelarab, MB., et al.[2020]

Regulatory dendritic cells (DCreg) can be generated in vitro and have the potential to reduce inflammation and improve outcomes in organ transplantation by promoting donor-specific immune tolerance.

A proposed phase I/II safety study will investigate the effects of donor-derived DCreg combined with standard immunosuppressive therapy on transplant rejection and immune responses in humans, building on successful results seen in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation. Thomson, AW., Zahorchak, AF., Ezzelarab, MB., et al.[2018]

Regulatory dendritic cells (DCregs) show promise as a novel cellular therapy for organ transplantation, with early-phase clinical trials indicating their feasibility and safety in kidney and liver transplants.

Preliminary results suggest that DCregs can reduce effector CD8+ T-cells and influence host immune responses, potentially leading to less reliance on traditional immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory dendritic cell therapy in organ transplantation. Hadjiyannis, Y., Thomson, AW.[2023]

Dendritic cells (DCs) play a crucial role in organ transplantation by balancing rejection and tolerance, and regulatory DCs (DCregs) show promise in promoting long-lasting organ-specific tolerance with fewer side effects compared to traditional immunosuppressive treatments.

Early-phase studies on DCreg therapy in living-donor kidney and liver transplants indicate potential safety and efficacy in inducing allograft tolerance, suggesting a new direction for improving transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulation of Regulatory Dendritic Cells for Induction Transplantation Tolerance. Que, W., Guo, WZ., Li, XK.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8215622/

Donor-derived regulatory dendritic cell infusion results ... Target DCreg doses (range 2.5–10 × 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg ...

2. science.org science.org/doi/10.1126/scitranslmed.adf4287

Donor-derived regulatory dendritic cell infusion modulates ... These data suggest that DCreg infusion could potentially reduce the extent of patient dependence on standard immunosuppressive regimens.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04208919

NCT04208919 | Delayed Infusion of DCreg in Living Donor ... Regulatory dendritic cells that were prepared from a donor leukapheresis will be infused into liver transplant recipients 7 days prior to the start of ...

4. journals.lww.com journals.lww.com/transplantjournal/abstract/2018/07001/regulatory_dendritic_cell__dcreg__cell_infusion_in.332.aspx

Regulatory Dendritic Cell (DCreg) Cell Infusion in Living... Based on strong preclinical data showing that regulatory dendritic cells (DCreg) of donor origin can promote long-term graft survival in rodents and suppress ...

5. stiresearch.health.pitt.edu stiresearch.health.pitt.edu/2022/09/29/sti-newsletter-regulatory-dendritic-cell-therapy-in-living-donor-liver-transplantation-a-first-in-human-trial/

STI Newsletter – Regulatory dendritic cell therapy in living ... The underlying hypothesis is that donor-derived DCreg administration a week before transplant to prospective adult living donor liver transplant recipients ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10932828/

Regulatory Dendritic Cell therapy in Organ Transplantation Recently, promising results from early-phase clinical testing of GMP-compliant DCregs in live donor kidney and liver transplantation were reported (Table 1).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33171019/

Donor-derived regulatory dendritic cell infusion results in host ... We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522086269

Donor-derived regulatory dendritic cell infusion results in ... We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver ...