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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new T-cell therapy, specifically Anti-viral T-cell Therapy by Gamma Capture, can combat viral infections like adenovirus, CMV, and EBV in individuals with weakened immune systems. The treatment uses special donor cells trained to target and destroy these viruses. Participants should have undergone a transplant or have a weakened immune system and a viral infection that persists despite standard treatments. The trial will assess the safety and effectiveness of this new approach. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from 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 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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that anti-viral T-cell therapy, like the one tested in this trial, is usually well-tolerated. In a study with 12 patients, 83.3% successfully received virus-specific T-cells without severe side effects. Other studies suggest that this therapy could help treat viral infections in people with weakened immune systems. Although this trial is still in the early stages, moving to a combined Phase 1/2 indicates some confidence in its safety based on earlier research. ^{1 2 3 4 5}

Why are researchers excited about this study treatment?

Unlike the standard of care for viral infections, which typically involves antiviral drugs that directly target the virus, the anti-viral T-cell therapy by gamma capture offers a unique approach by harnessing the body's immune system. This treatment uses viral-specific T-lymphocytes that are stimulated and captured using a special cytokine capture system, which targets viral antigens with greater precision. Researchers are excited because this method could provide a more targeted immune response, potentially improving effectiveness and reducing side effects associated with traditional antiviral therapies.

What evidence suggests that this anti-viral T-cell therapy by gamma capture is effective for viral infections?

Research has shown that anti-viral T-cell therapy, which participants in this trial will receive, can help fight viral infections. In one study with 34 patients, 21 improved after receiving this therapy. Another study found that patients typically had less virus in their bodies and felt better within 1 to 2 weeks after treatment. The positive effects of this therapy often last a long time. This treatment uses specially trained immune cells to target and fight specific viruses like adenovirus, CMV, and EBV. ^{1 3 6 7 8}

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

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]

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 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]

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]

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]

Citations

1. academic.oup.com academic.oup.com/jpids/article/13/Supplement_1/S49/7615748

Virus-Specific T Cells for the Treatment of Systemic Infections ... Improvement of viral load and/or symptoms is typically observed within 1–2 weeks from VST infusion. Responses are generally durable, with only ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06027879

NCT06027879 | Anti-viral T-cell Therapy by Gamma Capture 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10383098/

Virus-Specific T-Cell Therapy for Viral Infections of the Central ... Among the 34 patients, 21 showed a favorable clinical course following T-cell administration: 16 of them showed neurological improvement and 5 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06909110

NCT06909110 | Viral Specific T-Lymphocytes to Treat ... In this trial, we will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06027879/anti-viral-t-cell-therapy-by-gamma-capture

Anti-viral T-cell Therapy by Gamma Capture This trial will evaluate viral specific T cells generated by gamma capture technology. ... Primary Treatment: Specific T- Lymphocytes. Phase: 1/2.

6. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf302/8159933

Effectiveness and Safety of Autologous Virus-Specific T-Cell ... In this prospective study (N = 12), autologous virus-specific T cells (auto-VSTs) were successfully manufactured in 10 patients (83.3%).

7. sciencedirect.com sciencedirect.com/science/article/pii/S1600613524003472

Virus-specific T cell therapy to treat refractory viral ... This minireview will explore challenges and controversies in treating viral OIs, competing VST production methods, recently reported and ongoing clinical ...

8. nature.com nature.com/articles/s41467-024-54595-2

Compassionate access to virus-specific T cells for adoptive ... Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral ...