T-Lymphocytes for Viral Infections

Recruiting at 1 trial location

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, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

Duration: Up to 5 infusions with a minimum of 14-day intervals

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥2/6 HLA-matched, viral specific T cells have efficacy against adenovirus, CMV, and EBV, in subjects who have previously received any type of allogeneic HCT or solid organ transplant (SOT), or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. 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/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.

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.

What data supports the effectiveness of the treatment T-Lymphocytes for Viral Infections?

Research shows that using virus-specific T cells can help fight infections from viruses like cytomegalovirus, Epstein-Barr virus, and adenovirus, especially in people with weakened immune systems after stem cell transplants. Studies have found that these T cells can be safely and quickly produced and lead to significant reductions in viral infections, with a high success rate in clearing the viruses without causing harmful side effects. ^{1 2 3 4 5}

Is the use of virus-specific T lymphocytes safe for humans?

Research shows that using virus-specific T lymphocytes to treat infections like CMV, EBV, and adenovirus in immunocompromised patients is generally safe, with no immediate or delayed toxicities reported. ^{2 4 5 6 7}

How is the T-Lymphocytes treatment for viral infections different from other treatments?

This treatment is unique because it uses virus-specific T cells to target multiple viruses simultaneously, such as adenovirus, cytomegalovirus, and Epstein-Barr virus, especially in patients who have undergone stem cell transplants. Unlike traditional treatments, it involves a rapid generation of T cells without using viral components, making it safer and more feasible for widespread use. ^{1 4 5 7 8}

Research Team

Jessie Alexander, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for people with weakened immune systems due to a transplant or other reasons, who are battling infections from adenovirus, CMV, or EBV. Participants must have had an allogeneic HCT or solid organ transplant, or have compromised immunity and not responded well to standard treatments.

Inclusion Criteria

I have a persistent Adenovirus, CMV, or EBV infection despite treatment.

I, or my guardian, have signed the consent form. If I'm over 7, I've also agreed to participate.

I am between 1 month and 65 years old.

Exclusion Criteria

Patients who are pregnant or lactating.

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.

I received specific immune treatments recently and my T cell count is very low.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive viral specific T-Lymphocytes infusion to treat infection with adenovirus, CMV, or EBV

Up to 5 infusions with a minimum of 14-day intervals

Up to 5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including GvHD and adverse events

6 months post initial infusion, with additional 90 days if further infusions are received

Regular visits as per monitoring schedule

Data Abstraction

Data may be abstracted from subjects' medical charts for an additional 1 year after the most recent infusion

1 year

Treatment Details

Interventions

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

Trial Overview The study tests if T-cells that target specific viruses can fight off infections by adenovirus, CMV, and EBV in patients with weak immunity. It's a phase I/II trial using gamma capture technology to create these T-cells quickly and more affordably than current methods.

Participant Groups

Group I: Viral Specific T-Lymphocytes Experimental Treatment 3 Interventions

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec 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+

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]

A clinical-grade method was developed to isolate and expand adenovirus-specific T cells from donors, yielding an average of 3.4 million specific T lymphocytes from peripheral blood or leukapheresis products, which is crucial for restoring immunity in patients with lymphopenia after stem cell transplantation.

The generated T cell lines demonstrated effective responses against adenovirus-infected cells and showed reduced alloreactive proliferation, indicating their potential for safe and effective adoptive immunotherapy in combating ADV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Feuchtinger, T., Lang, P., Hamprecht, K., 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]

A new method allows for the rapid generation of virus-specific T cells targeting EBV, CMV, and adenovirus in just 2-3 weeks without using infectious viruses, making the process simpler and more accessible.

In a study involving 12 transplant recipients with active viral infections, 80% achieved complete virological responses, with no immediate or delayed toxicities observed, indicating both safety and efficacy of this T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Gerdemann, U., Katari, UL., Papadopoulou, A., et al.[2022]

Cytomegalovirus (CMV) reactivation poses significant risks for immunocompromised patients, such as those undergoing hematopoietic progenitor cell transplantation or living with HIV, leading to severe health complications despite antiviral treatments.

Recent advances in immunotherapy, including the adoptive transfer of CMV-specific T cell clones from seropositive donors, show promise in enhancing CMV-specific immunity and effectively treating CMV reactivation in these vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised patients. Lim, JB., Kwon, OH., Kim, HS., et al.[2005]

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. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. [2019]

4. 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]

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

Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. [2022]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised patients. [2005]

7. Netherlands pubmed.ncbi.nlm.nih.gov

[Immunological defense to viral infections: focus on virus-specific T cells]. [2007]

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

Simultaneous isolation of CD8(+) and CD4(+) T cells specific for multiple viruses for broad antiviral immune reconstitution after allogeneic stem cell transplantation. [2020]