BK CTL for Viral Infections

Recruiting at 8 trial locations

Overseen By Lauren Harrison

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: New York Medical College

Must not be taking: Steroids, Thymoglobulin, Alemtuzumab, others

Disqualifiers: Acute GVHD, HIV, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BK CTL (BK virus-specific cytotoxic T lymphocytes) to determine if it can safely and effectively reduce a specific virus in patients who have undergone a stem cell transplant or have certain immune system issues. The virus often resists standard antiviral medications. Suitable candidates for this trial have struggled with this viral infection despite other treatments or cannot tolerate the side effects of those treatments. Participants will receive up to five infusions of the BK CTL treatment, made from cells donated by another person. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like high-dose steroids or have had specific therapies recently. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that BK CTL is likely to be safe for humans?

Research has shown that a type of immune cell treatment, called BK virus-specific T-cells, is generally safe for patients. One study found that these T-cells helped control BK virus infections after certain stem cell transplants without causing serious side effects. Another study found this treatment to be a promising and safe option for managing these infections after kidney transplants. Overall, BK virus-specific T-cells have been used in other conditions and appear well-tolerated, meaning they are unlikely to cause major problems. These findings suggest that the treatment might be safe for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for BK viral infections, which typically include antiviral medications and supportive care, BK CTL therapy uses a cutting-edge approach by employing donor-derived cytotoxic T lymphocytes. These specialized immune cells are designed to specifically target and eliminate BK virus-infected cells, offering a more precise and potentially effective treatment option. Researchers are excited about BK CTL therapy because it harnesses the body's immune system to directly combat the virus, potentially leading to quicker and more sustained recovery compared to conventional therapies.

What evidence suggests that BK CTL might be an effective treatment for BK infection?

Research has shown that special immune cells, called BK cytotoxic T cells (CTLs), can help fight and reduce BK viral infections. Studies have found these virus-specific T cells useful in treating BK polyomavirus (BKPyV) infections in transplant recipients. This is important because untreated BK infections can lead to serious kidney problems. In past cases, patients who received these virus-specific T cells experienced improvements in their condition. In this trial, eligible patients with refractory BK infection will receive up to five infusions of BK CTLs, which may help lower the virus levels in those with difficult BK infections. ^{1 6 7 8 9}

Who Is on the Research Team?

Mitchell S Cairo, MD

Principal Investigator

New York Medical College

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults aged 0.1 to 30.99 years with stubborn BK virus infections after a stem cell or organ transplant or those with primary immunodeficiencies. Participants must have tried antiviral treatments without success or cannot tolerate them due to side effects like kidney damage.

Inclusion Criteria

I have a BK virus infection that hasn't improved with treatment or I can't tolerate the treatment.

I am a woman who can have children and my pregnancy test is negative.

Consent: Written informed consent given (by patient or legal representative) prior to any study-related procedures

Exclusion Criteria

Patients unwilling or unable to comply with the protocol or unable to give informed consent

Any medical condition which could compromise participation in the study according to the investigator's assessment

You are currently participating in another research study for treating a certain type of infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Eligible patients with refractory BK infection will receive up to 5 infusions of BK CTLs that are donor derived

12 weeks

Up to 5 visits (in-person) for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BK CTL

Trial Overview The study tests whether special immune cells called BK cytotoxic T cells (CTLs) can reduce the BK virus in patients who haven't responded well to other treatments post-transplantation or those with immune deficiencies.

How Is the Trial Designed?

Group I: BK CTL Experimental Treatment 1 Intervention

Eligible patients with refractory BK infection will receive up to 5 infusions of BK CTLs that are donor derived.

BK CTL is already approved in United States, European Union for the following indications:

Approved in United States as BK CTL for:

• Refractory BK infections post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT)
• Refractory BK infections in patients with primary immunodeficiencies (PID)

Approved in European Union as BK CTL for:

• Refractory BK infections post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT)
• Refractory BK infections in patients with primary immunodeficiencies (PID)

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 114 patients receiving EBV-specific cytotoxic T lymphocyte (CTL) infusions, the treatment showed minimal toxicity and effectively prevented EBV-related lymphoproliferative disease (LPD), with no cases in the 101 patients who received prophylaxis.

Among the 13 patients treated for existing LPD, 11 achieved sustained complete remissions, demonstrating the efficacy of CTLs in treating this condition, with functional CTLs persisting for up to 9 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Heslop, HE., Slobod, KS., Pule, MA., et al.[2023]

Virus-specific cytotoxic T lymphocytes (CTLs) play a crucial role in the immune response against viral infections by recognizing and eliminating virus-infected cells, which is essential for controlling infections like HIV and SIV.

Despite the strong activity of CTLs against HIV/SIV, the virus can persist and replicate due to the host's immune response failing to fully contain it, with certain HLA/MHC-I genotypes linked to the rate of AIDS progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of MHC-I genotypes with disease progression in HIV/SIV infections. Nomura, T., Matano, T.[2021]

A specific CTL clone (BK-20) was found to selectively kill Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) but not normal B lymphoblasts, indicating its potential for targeted therapy against certain cancer cells.

The study revealed that the sensitivity of Burkitt lymphoma lines to CTL lysis is influenced by their cellular phenotype, as only one of the EBV-infected sublines became sensitive to CTLs, highlighting the importance of cellular characteristics in immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation-dependent sensitivity of human B-cell-derived lines to major histocompatibility complex-restricted T-cell cytotoxicity. Torsteinsdottir, S., Masucci, MG., Ehlin-Henriksson, B., et al.[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]

A new method for expanding donor-derived EBV-specific cytotoxic T cells (CTLs) has been developed, allowing for the generation of over 80 million CTLs in 5 weeks, which is promising for clinical use in patients undergoing partially mismatched related donor (PMRD) transplantation.

These CTLs are highly specific to donor cells and do not attack recipient cells, showing potential for safe application in preventing EBV-induced lymphoma post-transplantation, while also demonstrating properties that enhance their survival and ability to migrate into tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro generation of Epstein-Barr virus-specific cytotoxic T cells in patients receiving haplo-identical allogeneic stem cell transplantation. Musk, P., Szmania, S., Galloway, AT., et al.[2019]

A new method was developed to measure how different types of immune cells, particularly T cells, respond to killing by cytotoxic T lymphocytes (CTLs), revealing that T cells are generally more susceptible to CTL-mediated killing than B or NK cells.

The study found that memory T cells, especially those marked by CCR5+ or HLA-DR+, are highly susceptible to CTL killing, which helps explain the loss of certain CD4 T cell subsets during chronic HIV infection and identifies potential targets for addressing viral reservoirs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential susceptibility of leukocyte subsets to cytotoxic T cell killing: implications for HIV immunopathogenesis. Liu, J., Roederer, M.[2007]

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]

Natural killer-cytotoxic T lymphocytes (NK-CTL) can effectively recognize and kill cells infected with cytomegalovirus (CMV) through a unique mechanism involving the HLA-E molecule, which allows them to bypass the usual immune evasion strategies of the virus.

This ability of NK-CTL to target not only CMV-infected cells but also allogeneic cells expressing certain HLA-Cw alleles raises concerns for transplantation, as it may lead to unwanted immune responses against transplanted tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-E-restricted recognition of human cytomegalovirus by a subset of cytolytic T lymphocytes. Romagnani, C., Pietra, G., Falco, M., et al.[2023]

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]

A new cellular immunotherapy approach was developed to reactivate BKV-specific cytotoxic T cells from kidney transplant recipients, which could help prevent BKV-associated interstitial nephritis, a serious complication after transplantation.

The reactivated T cells showed strong specificity for BKV-infected cells while sparing healthy cells, indicating a targeted and potentially safer treatment option for managing BKV infections in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK virus-specific cytotoxic T-cell lines in seropositive healthy individuals and renal transplant recipients. Comoli, P., Basso, S., Azzi, A., et al.[2022]

In a study of 77 adult patients after hematopoietic cell transplantation, those with BK virus reactivation had lower CD4 T-cell counts, indicating a potential link between T-cell immunity and BK virus disease.

The presence of BK virus-specific CD4 T cells producing Th1 cytokines was associated with lower rates of urinary symptoms, suggesting that these T cells play a crucial role in controlling BK virus reactivation and its clinical manifestations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BK virus-specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation. Espada, E., Cheng, MP., Kim, HT., et al.[2021]

The study involving 68 kidney transplant recipients (KTRs) found that BK virus (BKV)-specific T cell immunity, measured by the ELISPOT assay, is significantly higher in KTRs with cleared viremia compared to those with no viremia or ongoing BK viremia, suggesting a link between T cell response and viral clearance.

The results indicate that higher T cell responses in the controller group (those with less than 3 months of viremia) predict better outcomes, as they had significantly higher responses compared to the noncontroller group, highlighting the potential of the BKV-ELISPOT assay in predicting the risk of BK virus-associated nephropathy (BKVN).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of BK virus-specific interferon-γ enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients. Bae, H., Na, DH., Chang, JY., et al.[2021]

BKV-specific CD8(+) T cells are present in low frequencies in healthy individuals and have a unique memory phenotype, which suggests they may play a role in controlling BK virus reactivation in immunocompromised patients.

These T cells exhibit limited direct cytotoxic capacity but are polyfunctional, capable of producing key cytokines like IL-2 and IFN-γ, indicating their potential importance in antiviral immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotypic and functional characterization of circulating polyomavirus BK VP1-specific CD8+ T cells in healthy adults. van Aalderen, MC., Remmerswaal, EB., Heutinck, KM., et al.[2021]

The study identifies a method to effectively capture and expand BKV-specific CD4(+) T cells from kidney transplant patients, which is crucial for improving immune responses against BK virus reactivation.

BKV-specific CD4(+) T cells were found to be multifunctional and cytolytic, indicating their significant role in controlling BKV replication, thus highlighting their potential for use in adoptive immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of CD4(+) T cells in BKV-specific T cell immunity. Weist, BJ., Schmueck, M., Fuehrer, H., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33929874/

Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy ... BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. Methods: We ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S246802492401708X

Allogeneic CD4 T Cells Sustain Effective BK Polyomavirus ... We demonstrate that bp-BKPyVAN is associated with a loss of BKPyV-specific T cell proliferation, cytokine secretion, and cytotoxic capacities.

3. ashpublications.org ashpublications.org/bloodadvances/article/4/22/5745/474204/Virus-specific-T-cell-therapy-to-treat-BK

Virus-specific T-cell therapy to treat BK polyomavirus infection ... Key Points. Virus-specific T cells can be effectively used to treat BKPyV infections in HSCT and solid organ transplant recipients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10758681/

BK viral infection: A review of management and treatment - PMC BK viral infection is a significant post-transplant infection, which can result in kidney dysfunction if left unaddressed.

5. journals.lww.com journals.lww.com/transplantjournal/fulltext/2025/09000/donor_variability_and_pd_1_expression_limit_bk.18.aspx

Donor Variability and PD-1 Expression Limit BK... BK polyomavirus (BKPyV) nephropathy is a major cause of premature kidney transplant failure. Current management relies on reducing immunosuppression to restore ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/jmv.70357

A Phase I Study Evaluating Safety and Tolerability of Viral ... In summary, BK-specific T-cell therapy shows potential for being a safe strategy for managing BKPyV infections post-kidney transplantation to ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118718089

Safety and Efficacy of Virus-Specific Cytotoxic T- ... Safety and efficacy of virus-specific cytotoxic T-lymphocytes manufactured by the IFN-g cytokine capture system for the treatment of refractory adenovirus.

8. 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, 80 ...

9. journals.lww.com journals.lww.com/kidney360/fulltext/2021/05000/role_of_virus_specific_t_cell_therapy_for.18.aspx

Role of Virus-Specific T Cell Therapy for Cytomegalovirus... In this article, we review the emerging role of virus-specific T cell therapy in the management of CMV and BKV after kidney transplantation.