Virus-Specific T-Cell Therapy for Infections

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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests special immune cells designed to fight specific viruses in patients with weak immune systems or those who have had transplants. These patients have infections that don't respond to regular treatments. The donor immune cells help attack the viruses in their bodies. This approach has shown promise in enhancing immune responses to viruses like CMV and EBV.

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.

What data supports the effectiveness of the treatment Virus-Specific T-Cell Therapy for Infections?

Research shows that virus-specific T cells can effectively target and fight infections like cytomegalovirus, Epstein-Barr virus, and adenovirus, especially in patients with weakened immune systems. These T cells have been shown to restore antiviral immunity without causing harmful side effects, making them a promising treatment option. ^{1 2 3 4 5}

Is virus-specific T-cell therapy safe for humans?

Virus-specific T-cell therapy has been shown to be safe in humans, as it can restore antiviral immunity without causing acute toxicity or increasing the risk of graft-versus-host disease, especially in individuals who have undergone stem cell transplantation. ^{1 3 4 6 7}

How is the Virus-Specific T-Cell Therapy treatment different from other treatments for viral infections?

This treatment is unique because it uses virus-specific T cells (a type of immune cell) to target multiple viruses simultaneously, such as cytomegalovirus, Epstein-Barr virus, and adenovirus, which is particularly beneficial for patients with weakened immune systems. Unlike conventional treatments that often target only one virus and may lead to resistance, this therapy can provide broader and more effective antiviral protection. ^{1 2 3 4 5}

Research Team

Jessie Alexander, MD

Principal Investigator

Stanford University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

The pipeline of antiviral T-cell therapy: what's in the clinic and undergoing development. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

T cell therapies. [2019]

3. United States 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. [2013]

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

Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

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

6. Denmark pubmed.ncbi.nlm.nih.gov

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

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

Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. [2021]