VST Therapy for Post-Transplant Viral Infections

Overseen By Jamie Wilhelm, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Uncontrolled bacterial or fungal infection

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for viral infections that can occur after a solid organ transplant. It uses special cells called viral specific T-lymphocytes (VSTs), created from a participant's blood sample, to help fight these infections. The goal is to find a safer and more effective way to treat these infections while reducing the side effects of current treatments. People who have had a solid organ transplant and face challenging viral infections, such as those causing frequent hospital visits, might be a good fit for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that your clinical status must allow tapering of steroids to a certain level, so you might need to adjust your steroid dosage.

Is there any evidence suggesting that Viral Specific T-cells (VSTs) are likely to be safe for humans?

Research shows that Viral Specific T-cells (VSTs) are generally safe for people. Studies have found that the side effects of VST therapy are usually mild and manageable. These cells are specially designed to combat harmful viruses, particularly those that can attack the body after a transplant.

In past studies, most participants did not experience serious side effects from VST therapy. The mild side effects that did occur were typically treatable, suggesting that VSTs are well-tolerated and a promising option for treating viral infections post-transplant.

Additionally, VSTs have been studied for various viral infections and have demonstrated a good safety record. While more research is ongoing, current evidence supports the safety of using VSTs in individuals who have undergone a solid organ transplant. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for post-transplant viral infections, which often rely on antiviral drugs and immunosuppressants, Viral Specific T-cells (VSTs) offer a personalized approach by using the patient's own immune cells to target and fight the viruses. Researchers are excited about VSTs because they harness the body's natural immune response, potentially leading to fewer side effects and improved effectiveness compared to traditional antiviral medications. This treatment works by infusing patients with T-cells specifically trained to recognize and attack the viral infections, offering a targeted therapy that could enhance recovery and overall outcomes for patients.

What evidence suggests that Viral Specific T-cells (VSTs) might be an effective treatment for post-transplant viral infections?

Research has shown that viral specific T-lymphocytes (VSTs), which participants in this trial will receive, can effectively treat viral infections in organ transplant recipients. In one study, two kidney transplant patients with adenovirus (ADV) infections improved after just one VST treatment. VSTs are specially designed to target and fight specific viruses, helping to clear infections without the long-term use of antiviral drugs, which can have harmful side effects. Another study found that VST therapy lowered the risk of serious viral infections, suggesting it could be a safer and more effective treatment option. Overall, these findings indicate that VSTs could be a promising way to manage viral infections after transplants. ^{1 2 6 7 8}

Who Is on the Research Team?

Stella Davies, MBBS, PhD, MRCP

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for individuals of any age over 1 day who have had a solid organ transplant and are now experiencing viral infections. Participants must have specific levels of viruses in their blood or evidence of invasive viral infection, be able to reduce steroid use, and travel to Cincinnati for the VST infusion.

Inclusion Criteria

Blood EBV PCR ≥ 1,000

I have symptoms or test results suggesting EBV-related lymph node issues.

Evidence of invasive adenovirus infection defined as the presence of adenoviral positivity as detected by PCR or culture from one site such as stool or blood or urine or nasopharynx. Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture or PCR from more than 2 sites such as stool or blood or urine or nasopharynx.

Exclusion Criteria

I do not have any untreated bacterial or fungal infections.

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-lymphocytes (VSTs) to treat viral infections post solid organ transplant

4 weeks

Prolonged treatments with intravenous anti-viral medications

Follow-up

Participants are monitored for the presence of viral-specific T-cells and safety after treatment

4 weeks

Assessment at 30 days after infusion

What Are the Treatments Tested in This Trial?

Interventions

• Viral Specific T-cells (VSTs)

Trial Overview The study tests Viral Specific T-cells (VSTs) as a treatment for post-transplant viral infections. These cells are engineered from the participant's blood to combat viruses that can cause complications after an organ transplant.

How Is the Trial Designed?

Group I: Viral Specific T-cells (VSTs) Experimental Treatment 1 Intervention

Viral Specific T-cells (VSTs) is already approved in United States, European Union for the following indications:

Approved in United States as Posoleucel for:

• Adenovirus infections
• BK virus infections
• Cytomegalovirus infections
• Epstein-Barr virus infections
• Human herpes virus-6 infections
• JC virus infections

Approved in European Union as Posoleucel for:

• Adenovirus infections
• BK virus infections
• Cytomegalovirus infections
• Epstein-Barr virus infections
• Human herpes virus-6 infections
• JC virus infections

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Hoxworth Blood Center

Collaborator

Trials

7

Recruited

1,600+

Published Research Related to This Trial

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]

Adoptive immunotherapy using virus-specific T cells (VSTs) has been shown to be a safe and effective treatment for viral infections in patients who have undergone hematopoietic stem cell transplantation (HSCT), with minimal toxicity and a low risk of graft versus host disease.

VSTs have demonstrated efficacy against several viral infections, including cytomegalovirus and Epstein-Barr virus, highlighting their potential as a therapeutic option during the immune deficient period following HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications of virus-specific T cell therapies post-BMT. Motta, CM., Keller, MD., Bollard, CM.[2023]

In a study involving 36 patients with primary immunodeficiencies (PIDs), virus-specific T lymphocytes (VSTs) demonstrated an 81% response rate in treating viral infections, indicating their efficacy in this vulnerable population.

The overall survival rate at 6 months post-VST therapy was 80%, suggesting that VSTs are not only effective but also safe, with manageable adverse effects such as graft-versus-host disease in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. Naik, S., Nicholas, SK., Martinez, CA., et al.[2023]

Adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs) has emerged as a promising immunotherapeutic approach to effectively combat viral infections after hematopoietic stem cell transplantation (HSCT), offering a way to restore antiviral immunity without causing graft-versus-host disease.

This review highlights the potential of VSTs to improve outcomes for patients suffering from life-threatening viral infections post-transplant and discusses strategies to expand their use beyond individual patient products and into other viral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-Specific T Cells: Broadening Applicability. Barrett, AJ., Prockop, S., Bollard, CM.[2021]

In a phase II clinical trial involving 38 patients, the use of banked virus-specific T cells (VSTs) showed a remarkable 92% overall response rate in treating severe viral infections after hematopoietic stem-cell transplantation, with complete responses for BKV and EBV infections.

The treatment was safe, with only two mild cases of graft-versus-host disease reported, and the VSTs demonstrated persistence for up to 12 weeks, providing broad antiviral protection against multiple viral pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation. Tzannou, I., Papadopoulou, A., Naik, S., et al.[2022]

A third-party virus-specific T cell (VST) bank was successfully established using discarded white cells from blood donors, showing significant cytotoxicity against multiple viruses like Adenovirus and Cytomegalovirus, which are often difficult to treat.

The study demonstrated that a carefully selected combination of just 6 VST lines could provide coverage for 99% of potential recipients in a multi-ethnic Asian population, indicating a cost-effective approach to enhance treatment options for opportunistic viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost-effective strategy for selection of third-party donors for a virus-specific T-cell bank for an Asian patient population. Linn, YC., Sundar Raj, K., Teo, B., et al.[2023]

Virus-specific T-cell (VST) therapy offers a promising alternative to traditional antiviral agents, as it can effectively treat viral infections without causing drug resistance or significant toxicity, particularly in patients who are unresponsive to other treatments after hematopoietic cell transplantation (HCT).

Studies have shown that VST therapy is effective against various viruses, including herpes and polyomaviruses, and can be safely administered without causing severe graft-versus-host disease (GVHD), suggesting its potential for broader use in treating opportunistic infections in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for refractory viral infections]. Morio, T., Fujita, Y., Takahashi, S.[2019]

Adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs) has emerged as a promising immunotherapeutic approach to effectively combat viral infections after hematopoietic stem cell transplantation (HSCT), addressing the limitations of conventional antiviral drugs.

This method not only helps reconstitute antiviral immunity without causing graft-versus-host disease but also shows potential for broader application beyond individual patients and for treating other viral infections outside of HSCT contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reprint of: Virus-Specific T Cells: Broadening Applicability. Barrett, AJ., Prockop, S., Bollard, CM.[2020]

Posoleucel, a multivirus-specific T-cell therapy, was found to be safe and well tolerated in a phase II trial involving 58 allo-HCT recipients, with no severe infusion-related toxicities reported.

The therapy demonstrated a high overall response rate of 95% and a significant median plasma viral load reduction of 97% within 6 weeks, effectively treating refractory viral infections in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting. Pfeiffer, T., Tzannou, I., Wu, M., et al.[2023]

The study successfully produced virus-specific T cells (VST) in 100% of cases using the CliniMACS Prodigy® system, demonstrating a feasible and automated method for therapy that could enhance scalability.

In a retrospective analysis of 26 patients with viral diseases post-hematopoietic stem cell transplantation, VST therapy showed a 77% response rate, significantly improving overall survival for responders compared to non-responders (P<0.001), with a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation. Heinz, AT., Calkoen, FGJ., Derbich, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37910558/

Viral specific T cell therapy in kidney transplant recipients We describe our experience of using the virus-specific T cell therapy ... Results: Two cases of ADV infection resolved after one infusion of VSTs.

2. 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 ...

3. ashpublications.org ashpublications.org/bloodadvances/article/7/10/2105/493725/Outcomes-following-posttransplant-virus-specific-T

Outcomes following posttransplant virus-specific T-cell therapy ... Virus-specific T cells are safe in patients with SCD following hematopoietic stem cell transplant. In patients with active viremia, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11413696/

Final outcomes from a phase 2 trial of posoleucel in ... The multivirus-specific T-cell therapy posoleucel appeared to reduce the risk of clinically significant viral infections.

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

Virus-Specific T Cells for the Treatment of Systemic Infections ... This article provides a practical guide to VST therapy by reviewing manufacturing techniques, donor selection, and treatment indications.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6750917/

Adverse Effects of Virus-Specific T-Cell Therapy Studies reviewed indicate that the adverse effects associated with VST therapy are limited and generally treatable.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36628536/

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T ... Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03180216

T-Lymphocytes for Prevention or Treatment of Viral ... This Phase I dose-escalation trial is designed to evaluate the safety of rapidly generated multivirus-specific T-cell products with antiviral activity ...