Tolerogenic Dendritic Cell Vaccine for Type 1 Diabetes

Overseen By Study Coordinator

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Insulin

Must not be taking: Corticosteroids, Immunosuppressives, Monoclonals, others

Disqualifiers: Organ transplant, Malignancy, Infections, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

6 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as systemic corticosteroids, systemic immunosuppressive therapy, and insulin sensitizers, before joining. Over-the-counter anti-inflammatory drugs like ibuprofen are generally allowed, but chronic use during study visits is not permitted.

What data supports the effectiveness of the treatment PIpepTolDC for Type 1 Diabetes?

Research shows that tolerogenic dendritic cells (tDC) can make the immune system less reactive to specific proteins involved in Type 1 Diabetes, potentially helping to control the disease. In studies, tDCs reduced the activity of immune cells that attack insulin-producing cells, suggesting they might be useful for some patients with Type 1 Diabetes. ^{1 2 3 4 5}

Is the Tolerogenic Dendritic Cell Vaccine safe for humans?

The safety of tolerogenic dendritic cells (tDC) has been demonstrated in phase I clinical studies, showing they are generally safe for humans. These studies have been conducted in the context of type 1 diabetes and other autoimmune conditions. ^{1 4 6 7 8}

How is the treatment PIpepTolDC different from other treatments for Type 1 Diabetes?

PIpepTolDC is unique because it uses tolerogenic dendritic cells to specifically target and inactivate the immune cells that mistakenly attack insulin-producing cells in the pancreas, potentially reducing the autoimmune response without affecting the rest of the immune system. This approach is different from standard treatments that mainly focus on managing blood sugar levels rather than addressing the underlying autoimmune cause. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial investigates the side effects of PIpepTolDC vaccine in treating patients with type 1 diabetes who use insulin and don't have any other diabetes-related health complications. Type 1 diabetes is an autoimmune disease. This means that the immune system, which usually protects against foreign invaders like bacteria and viruses, attacks the body's insulin-producing betacells in the pancreas (autoimmune response). Overtime, the beta cells are destroyed by the immune system. To stay alive, people with type 1 diabetes must use insulin. PIpepTolDC vaccine is a type of immunotherapy (a treatment that uses a person's own immune system) that works like an allergy shot. The vaccine is made using one's own immune cells (dendritic cells) and a beta cell protein. The vaccine may teach the immune system to stop attacking the beta cells, which may help the beta cells recover and make enough insulin to control blood sugar levels. The vaccine may also help reduce future type 1 diabetes related complications.

Research Team

Behrouz Salehian-Dardashti, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for people with type 1 diabetes who use insulin, have stable blood sugar control, and no other diabetes complications. They must be willing to undergo a procedure to collect immune cells and not have certain genetic traits or previous severe allergic reactions.

Inclusion Criteria

My organs are functioning well.

I do not have diabetes-related complications like kidney, eye, or nerve damage.

I am eligible for a procedure to collect my own cells.

Exclusion Criteria

I have a history of HIV, hepatitis B, hepatitis C, HTLV, or syphilis.

I am not on any prescription anti-inflammatory drugs, but I may use OTC like ibuprofen or Tylenol.

I haven't taken diabetes medication that stimulates insulin production in the last 2 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Participants undergo leukapheresis to collect CD14+ monocytes for vaccine preparation

1 day

1 visit (in-person)

Treatment

Participants receive a prime dose of PIpepTolDC intradermally on Day 0, followed by a boost dose on Day 28

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Treatment Details

Interventions

• PIpepTolDC

Trial Overview The PIpepTolDC vaccine, an immunotherapy made from the patient's own immune cells mixed with a beta cell protein, is being tested. It aims to retrain the immune system to stop attacking pancreatic beta cells in type 1 diabetics.

Participant Groups

Group I: Autologous Tolerogenic Dendritic Cell with Proinsulin Peptide (PIpepTolDC) Experimental Treatment 1 Intervention

After completion of leukapheresis, patients receive a prime dose of PIpepTolDC intradermally (ID) on Day 0, followed by a boost dose of PIpepTolDC ID on Day 28.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

References

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

Tolerogenic dendritic cells induce antigen-specific hyporesponsiveness in insulin- and glutamic acid decarboxylase 65-autoreactive T lymphocytes from type 1 diabetic patients. [2014]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerogenic Dendritic Cells and T-Regulatory Cells at the Clinical Trials Crossroad for the Treatment of Autoimmune Disease; Emphasis on Type 1 Diabetes Therapy. [2020]

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

Dendritic cell therapy for Type 1 diabetes suppression. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Dendritic cell subsets and type I diabetes: focus upon DC-based therapy. [2006]

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

Infectious tolerance as candidate therapy for type 1 diabetes: transfer of immunoregulatory properties from human regulatory T cells to other T cells and proinflammatory dendritic cells. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerogenic dendritic cells in type 1 diabetes: no longer a concept. [2023]

7. Singapore pubmed.ncbi.nlm.nih.gov

Dendritic cell-targeted pancreatic beta-cell antigen leads to conversion of self-reactive CD4(+) T cells into regulatory T cells and promotes immunotolerance in NOD mice. [2021]

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

Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. [2022]