Virus-Specific T-Cell Therapy for Infections

Not currently recruiting at 2 trial locations

Overseen By Jessie Barnum, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jessie L. Alexander

Must not be taking: ATG, Alemtuzumab

Disqualifiers: Acute GVHD, Chronic GVHD, Relapse, others

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

Compensation: Varies

Number of Visits: 5

Duration: Up to 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using virus-specific T-cells to combat infections like adenovirus and CMV in individuals with weakened immune systems. It targets those who have undergone a transplant or are on medications that reduce immunity and continue to struggle with these infections despite standard treatments. The trial evaluates whether these specially prepared T-cells can safely and effectively address the infections. For individuals who have had a transplant and are still battling adenovirus or CMV despite treatment, this trial may be suitable. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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 must 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 trial's treatments are likely to be safe?

Research has shown that T-cell therapies targeting specific viruses can be safe and effective for individuals with weakened immune systems, such as those who have undergone organ or stem cell transplants. For instance, one study found that T-cells targeting adenovirus were safe and effective for individuals with challenging infections following a stem cell transplant. Similarly, research on T-cells targeting cytomegalovirus (CMV) found them to be safe for transplant patients, aiding in protection against CMV and other serious infections.

Regarding Epstein-Barr virus (EBV)-specific T-cells, evidence suggests they can safely help reduce the virus in transplant recipients. Previous research has demonstrated that these treatments are generally safe, meaning patients tolerate them well. The use of these T-cells has shown promise without causing major side effects. While this trial continues to test the treatments, existing studies suggest these therapies have a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Virus-Specific T-Cell Therapy because it offers a targeted approach to fighting viral infections by harnessing the body's own immune system. Unlike standard antiviral drugs, which often work by directly inhibiting viral replication, this therapy uses specially trained T-lymphocytes that are designed to specifically recognize and attack cells infected with adenovirus, cytomegalovirus, and Epstein-Barr virus. These T-cells are collected from a donor and stimulated in a lab to enhance their virus-targeting abilities, then reintroduced to the patient’s body to bolster their immune response. This method aims to provide a more precise and potentially faster-acting treatment by directly enhancing the body's natural defenses against these viruses.

What evidence suggests that this trial's treatments could be effective for adenovirus and CMV infections?

This trial will evaluate the effectiveness of virus-specific T-cell therapy for infections. Research has shown that virus-targeting T-cells hold promise for fighting infections like adenovirus and CMV (cytomegalovirus) in individuals with weakened immune systems. For adenovirus, studies indicate these T-cells perform very well, particularly in patients who have undergone stem cell transplants. Approximately two-thirds of patients with CMV have experienced complete virus removal. The treatment is generally safe and boasts high success rates. For Epstein-Barr Virus (EBV), T-cell therapy has led to significant survival rates and effective virus control. Overall, these virus-specific T-cells have demonstrated good results in managing ongoing viral infections in vulnerable patients. Participants in this trial will receive viral-specific T-lymphocytes to assess their effectiveness in treating these infections. ^{1 6 7 8 9}

Who Is on the Research Team?

Jessie Alexander, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for people aged 1 month to 60 years who have had a bone marrow or organ transplant, or have compromised immunity due to other conditions. They must be struggling with infections from adenovirus, CMV, or EBV despite standard treatments. Women of childbearing age need a negative pregnancy test.

Inclusion Criteria

I am not pregnant or have been surgically sterilized.

I have had a stem cell or organ transplant, have a primary immunodeficiency, or am on immunosuppressive therapy.

Patient, parent, or legal guardian must have given written informed consent, according to FDA guidelines

Exclusion Criteria

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

I have ongoing severe chronic graft-versus-host disease.

Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks to participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study

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 infusions to treat adenovirus or CMV

Up to 10 weeks

Up to 5 infusions, minimum 14-day intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Extended Follow-up

Additional monitoring for GvHD and adverse events if additional infusions are received

90 days from last infusion

What Are the Treatments Tested in This Trial?

Interventions

• Adenovirus Specific T-Lymphocytes
• Cytomegalovirus Specific T-Lymphocytes
• Epstein-Barr Virus Specific T-Lymphocytes

Trial Overview The study tests if special immune cells called viral specific T-lymphocytes can fight off persistent infections by adenovirus, CMV, and EBV in those with weakened immune systems from transplants or other causes.

How Is the Trial Designed?

Group I: Viral Specific T-Lymphocytes Experimental Treatment 2 Interventions

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?

Jessie L. Alexander

Lead Sponsor

Trials

1

Recruited

30+

Jessie Barnum

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Virus-specific T cells can effectively target multiple pathogens in patients who have undergone hematopoietic stem cell transplantation, showing promise against viruses like cytomegalovirus and Epstein-Barr Virus.

The potential to target additional pathogens such as BK virus, JC virus, and Zika virus suggests that this therapy could be expanded to improve patient outcomes, especially with the development of patient-specific and third-party T cell products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pipeline of antiviral T-cell therapy: what's in the clinic and undergoing development. Fatic, A., Zhang, N., Keller, MD., et al.[2022]

Adoptive immunotherapy using virus-specific T lymphocytes can effectively restore immunity against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) without causing acute toxicity or increasing the risk of graft-versus-host disease, making it a safe treatment option.

In a study of 204 healthy donors, significant variations in T cell frequencies were found, with 100% of CMV-seropositive donors showing specific T cells, indicating that targeting specific antigens like CMVpp65 and EBVBZLF1 could enhance the efficacy of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMV-, EBV- and ADV-specific T cell immunity: screening and monitoring of potential third-party donors to improve post-transplantation outcome. Sukdolak, C., Tischer, S., Dieks, D., et al.[2013]

A new method allows for the rapid generation of polyclonal cytotoxic T lymphocytes (CTLs) that target 15 different viral antigens from 7 viruses, which are common causes of severe infections after hematopoietic stem cell transplantation, in just 10 days.

This approach enhances the effectiveness of CTLs by reducing competition between antigens and increasing the variety of virus-specific T cells, making it a promising and cost-effective alternative to traditional antiviral treatments for transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Gerdemann, U., Keirnan, JM., Katari, UL., et al.[2021]

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]

Polyclonal Epstein-Barr virus (EBV)-specific cytotoxic T cells (CTL) have shown promise in treating EBV-associated malignancies, indicating their potential effectiveness in targeting specific cancers.

The chapter discusses strategies to enhance the antitumor activity of these EBV-specific CTLs, which could lead to improved T cell therapies for various tumors with known antigens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell therapies. Gottschalk, S., Bollard, CM., Straathof, KC., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8525242/

Virus-specific T cells for adenovirus infection after stem ... Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725003677

Outcome Analysis Post Virus-Specific T Cell Therapy for ... VST therapy is generally well-tolerated and effective against adenovirus in pediatric patients post-HCT. This study represents one of the largest pediatric ...

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

Virus-Specific T Cells for the Treatment of Systemic Infections ... VSTs have proven highly effective for the treatment of CMV viremia with complete viral clearance observed in about two-thirds of cases. Similar ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34473237/

Virus-specific T cells for adenovirus infection after stem ... These data suggest that VSTs are a highly safe and effective therapy for the management of adenoviral infection in immunocompromised hosts.

5. ashpublications.org ashpublications.org/bloodadvances/article-abstract/5/17/3309/476675

Virus-specific T cells for adenovirus infection after stem cell ... Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723023564

604 Adenoviral Cellular Therapy with Adenovirus (ADV)- ... Preliminary data affirm that donor ADV-specific CTLs are safe and effective in treating refractory ADV cases post-AlloHSCT.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11806872/

Adenovirus‐Specific T Cells in Adults Are Frequent, Cross‐ ... Adenovirus‐Specific T Cells in Adults Are Frequent, Cross‐Reactive to Common Childhood Adenovirus Infections and Boosted by Adenovirus‐Vectored ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4836/505411/Treatment-of-Refractory-Adenovirus-ADV-Infections

Treatment of Refractory Adenovirus (ADV) Infections Using ... From the Viral Cytotoxic T-Lymphocyte Consortium (VIRCTLC), we present safety and efficacy results on immune compromised, AlloHSCT, or SOT ...

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

Compassionate access to virus-specific T cells for adoptive ... We and others have shown that autologous T cell therapy can be generated from both SOT and HSCT recipients, demonstrating a good safety profile ...