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

42 Participants Needed

Trial Summary

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.

What data supports the effectiveness of this treatment for post-transplant viral infections?

Research shows that virus-specific T-cell (VST) therapy, like Posoleucel, is promising for treating viral infections after stem cell transplants, especially when other treatments fail. VSTs can help fight multiple viruses without causing severe side effects, making them a valuable option for patients with weakened immune systems. ^{1 2 3 4 5}

Is VST Therapy safe for humans?

VST Therapy, also known as Posoleucel or Tabelecleucel, has been shown to be generally safe in humans, with minimal side effects reported in clinical trials. Most studies report only mild adverse events, and the therapy has a low risk of causing graft-versus-host disease (a condition where the donor cells attack the recipient's body). ^{1 4 6 7 8}

How is VST therapy different from other treatments for post-transplant viral infections?

VST therapy is unique because it uses virus-specific T-cells to boost the immune system's ability to fight viral infections after a transplant, without causing drug resistance or severe side effects like graft-versus-host disease. Unlike traditional antiviral drugs, which can be toxic and expensive, VSTs are derived from donors and can provide long-lasting protection against a wide range of viruses. ^{2 3 5 9 10}

What is the purpose of this trial?

The purpose of this research study is to learn more about the use of viral specific T-lymphocytes (VSTs) to treat viral infections that may happen after solid organ transplant (SOT). VSTs are cells specially designed to fight viral infections that may happen after a solid organ transplant. These cells are created from a blood sample collected from the study participant. Solid organ transplant and the use of immunosuppressive medications reduces the body's ability to fight infections. Viral infections are a common problem after transplant and can cause significant complications. Reduction of immunosuppression may put the organ at risk of rejection. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find a better way to treat these infections and minimize complications.

Research Team

Stella Davies, MBBS, PhD, MRCP

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

[Immunotherapy for refractory viral infections]. [2019]

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

Identification of the best-suited donor for generating virus-specific T cells. [2020]

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

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. [2023]

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

Virus-Specific T Cells: Broadening Applicability. [2021]

6. United States 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. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation. [2023]

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

Applications of virus-specific T cell therapies post-BMT. [2023]

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

Reprint of: Virus-Specific T Cells: Broadening Applicability. [2020]

10. England 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. [2023]