Specific T-Lymphocytes for Viral Infections

(Gamma Capture Trial)

Overseen By Paul Szabolcs, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Paul Szabolcs

Must not be taking: Antithymocyte globulin, Alemtuzumab

Disqualifiers: Acute GVHD, Uncontrolled malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥1/6 Human Leukocyte Antigens (HLA) -matched, viral specific T cells have efficacy against adenovirus, Cytomegalovirus (CMV), and Epstein Barr Virus (EBV) in subjects who have previously received any type of allogeneic Hematopoietic Cell transplant (HCT) or solid organ transplant (SOT) or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. This trial will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that your steroid dose should be reduced to less than 1 mg/kg/day of prednisone (or equivalent) before receiving the cellular infusion.

Is T-cell therapy generally safe for humans?

T-cell therapies, including those for viral infections, have shown promise but can cause side effects ranging from mild to severe, such as cytokine release syndrome (a strong immune response) and neurological issues. Safety measures, like a cellular safety switch, are being developed to manage these risks. ^{1 2 3 4 5}

How is the treatment Anti-viral T-cell Therapy by Gamma Capture different from other treatments for viral infections?

This treatment is unique because it involves the adoptive transfer of virus-specific T cells, which are immune cells tailored to target and eliminate specific viruses. Unlike traditional antiviral drugs, this therapy aims to restore the body's own immune response by using T cells that are expanded and modified outside the body, potentially offering a more targeted and long-lasting solution to viral infections. ^{6 7 8 9 10}

Who Is on the Research Team?

Paul Szabolcs, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for people aged 1 month to 65 years who've had a bone marrow or organ transplant, have compromised immunity, and are battling persistent infections from adenovirus, CMV, or EBV despite standard treatments. They must not be pregnant or breastfeeding and should agree to use birth control if applicable.

Inclusion Criteria

I have an Epstein-Barr virus infection or disease.

My adenovirus levels are high despite 2 weeks of antiviral treatment.

I have a persistent Adenovirus, CMV, or EBV infection despite treatment.

Exclusion Criteria

If you have any other medical issues not mentioned here that the doctor thinks might make it risky for you to participate, make it difficult for you to follow study rules, or affect the accuracy of the study results, you may not be able to join.

I am not breastfeeding.

I have moderate to severe graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive viral specific T cells generated by gamma capture technology. Infusions are given with a minimum of 14 days apart, up to a total of 6 infusions.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including GVHD and adverse events for a minimum of three months from the last infusion.

6 months

Extended Follow-up

Data may be abstracted from subjects' medical charts for an additional 1 year after the most recent viral-specific T cell infusion.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Anti-viral T-cell Therapy by Gamma Capture

Trial Overview The study tests the effectiveness of T-cells treated with gamma capture technology against viral infections in patients with weakened immune systems due to transplants or other conditions. It's a phase I/II trial assessing safety and how well these cells fight off specific viruses.

How Is the Trial Designed?

Group I: Viral Specific T-Lymphocytes Experimental Treatment 1 Intervention

Viral Specific T-Lymphocytes Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.

Who Is Running the Clinical Trial?

Paul Szabolcs

Lead Sponsor

Trials

8

Recruited

230+

Published Research Related to This Trial

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

Adoptive T-cell therapy shows promise for treating various cancers and infections, but safety concerns remain due to potential on-target and off-target toxicities, which can sometimes be fatal.

The inducible caspase 9 (iCasp9) safety switch offers a solution by allowing for the rapid elimination of modified T cells if adverse effects occur, enhancing the safety of T-cell therapies, especially in cases like graft-versus-host disease in stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy: adverse events and safety switches. Tey, SK.[2022]

Adoptive cell therapy (ACT) has shown significant benefits in treating cancer, but it is associated with a range of toxicities, including cytokine release syndrome and neurological toxicity, which can be mild to life-threatening.

The review highlights the need for improved management strategies for these toxicities to enhance the safety of ACT treatments while maintaining their therapeutic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The toxicity of cell therapy: Mechanism, manifestations, and challenges. Jin, Y., Dong, Y., Zhang, J., et al.[2021]

The study successfully isolated and expanded cytomegalovirus-specific CD8+ T cell clones from bone marrow donors, demonstrating the feasibility of using adoptive T cell transfer for human therapy.

After transferring these T cell clones to immunodeficient bone marrow transplant recipients, there was no observed toxicity, and the T cells provided a lasting immune response against cytomegalovirus, indicating their potential effectiveness in treating viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Riddell, SR., Watanabe, KS., Goodrich, JM., et al.[2023]

Patients receiving hematopoietic stem cell transplants are at a high risk for viral infections like cytomegalovirus and EB virus due to severe immunosuppression, which can lead to significant health complications.

Recent advancements in generating virus-specific T cells, such as using peptide-HLA multimers and third-party donor banks, have improved the feasibility and speed of T-cell therapy, making it a promising approach for treating viral infections in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy using T cells for treating viral infections]. Takahashi, S.[2019]

In a study involving 25 patients who underwent related-donor transplantation, the direct isolation and administration of cytomegalovirus-specific T cells successfully restored antiviral immunity, demonstrating feasibility and effectiveness in a clinical setting.

The infused T cells expanded rapidly in the patients, predominantly consisting of CD4(+) and CD8(+) effector-memory cells, and provided protection against reinfection in most cases, highlighting their potential for broader application in cellular therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Peggs, KS., Thomson, K., Samuel, E., et al.[2022]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. [2023]

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

The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care. [2022]

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

T-cell adoptive immunotherapy using tumor-infiltrating T cells and genetically engineered TCR-T cells. [2018]

4. Australia pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy: adverse events and safety switches. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The toxicity of cell therapy: Mechanism, manifestations, and challenges. [2021]

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

Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. [2023]

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

Principles for adoptive T cell therapy of human viral diseases. [2016]

8. Japan pubmed.ncbi.nlm.nih.gov

[Immunotherapy using T cells for treating viral infections]. [2019]

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

Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. [2022]

10. Denmark pubmed.ncbi.nlm.nih.gov

Immunotherapy with virus-specific cytotoxic T lymphocytes after organ transplantation. [2006]