Genetically Modified T-cells for Infections in Cancer Patients

Overseen By May Daher, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-thymocyte globulin, Campath

Disqualifiers: Uncontrolled infections, Active GVHD, 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: Unknown

Duration: 16 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment using specially modified immune cells, called virus-specific cytotoxic T-lymphocytes (CTLs), to combat infections in cancer patients with weakened immune systems. The CTLs target and destroy specific viruses such as adenovirus, BK virus, cytomegalovirus, JC virus, and COVID-19. This trial suits patients who have undergone a stem cell transplant and face viral infections matching those mentioned, or those with COVID-19-related lung issues. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you've received anti-thymocyte globulin within 14 days or donor lymphocyte infusion or campath within 28 days. Also, you cannot be on immunosuppressive therapy other than tacrolimus, sirolimus, or steroids.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain immunosuppressive therapies other than tacrolimus, sirolimus, or steroids, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that virus-specific cytotoxic T-lymphocytes (CTLs), a type of immune cell that fights certain viruses, are generally safe. One study tested these cells in adults at high risk for COVID-19, and the treatment showed no major safety issues across four different doses.

Another study examined the use of CTLs for treating adenovirus infections and found the treatment both safe and effective in managing the virus. These findings suggest that while the treatment remains under study, it appears safe so far.

This trial is in an early stage, focusing on assessing the safety and practicality of the treatment for people. Although early trials do not fully confirm safety, they help identify potential risks and evaluate how well people tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Virus-specific Cytotoxic T-lymphocytes (CTLs) are unique because they harness the body's immune system to target and destroy virus-infected cells in cancer patients. Unlike standard antiviral drugs, which can have limited effectiveness and broad side effects, these genetically modified T-cells are designed to specifically attack viruses without harming healthy cells. Researchers are excited because this targeted approach could offer a more effective and safer option for managing viral infections in vulnerable cancer patients. Additionally, the possibility of receiving multiple infusions allows for ongoing treatment adaptability based on patient response.

What evidence suggests that virus-specific cytotoxic T-lymphocytes might be an effective treatment for viral infections in cancer patients?

Research has shown that special immune cells, called virus-specific T cells, can help treat viral infections in cancer patients. In one study, more than 70% of patients with viral infections after a transplant experienced complete or partial improvement after receiving these cells. Another study found that researchers successfully created these virus-targeting T cells for 83.3% of patients, suggesting their potential effectiveness. In this trial, participants will receive virus-specific cytotoxic T-lymphocytes (CTLs) designed to combat infections from viruses like adenovirus, CMV, and COVID-19. These T cells locate and destroy the virus causing the infection, which can help reduce symptoms and improve health outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

May Daher, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with blood cancers and certain viral infections (ADV, BKV, CMV, JCV, COVID-19) after stem cell transplant or with pneumonia from COVID-19. They must be able to consent and agree to long-term follow-up. Women who can have children should use two birth control methods during the study.

Inclusion Criteria

I have symptoms and tested positive for BKV in my blood or urine.

You have had a specific type of stem cell transplant in the past that makes you ineligible for the trial if you have certain infections.

I have tested positive for adenovirus in my blood or have symptoms of adenovirus organ disease.

Exclusion Criteria

I have GVHD that hasn't responded to steroid treatment.

I haven't received ATG in the last 14 days or DLI/campath in the last 28 days.

I do not have any uncontrolled infections, or if I do, they are improving with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive virus-specific CTLs intravenously over 30 minutes. Patients may receive up to 8 additional infusions with at least 2 weeks between each infusion.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Virus-specific Cytotoxic T-lymphocytes

Trial Overview The trial tests genetically engineered virus-specific T-cells designed to fight specific viruses causing infections in cancer patients with weakened immune systems. It aims to see if these modified cells are safe and effective at controlling the infection.

How Is the Trial Designed?

Group I: Treatment for viral infections (virus-specific CTLs) Experimental Treatment 1 Intervention

Patients receive virus-specific CTLs intravenously (IV) over 30 minutes. Patients with partial response, stable disease, or progressive disease may receive up to 8 additional infusions of virus-specific CTL at least 2 weeks between each infusion.

Virus-specific Cytotoxic T-lymphocytes is already approved in United States, European Union for the following indications:

Approved in United States as Posoleucel (Viralym-M, ALVR105) for:

• Adenovirus infections
• BK virus infections
• Cytomegalovirus infections
• Epstein-Barr virus infections
• Human herpesvirus-6 infections
• JC virus infections

Approved in European Union as Posoleucel (Viralym-M, ALVR105) for:

• Adenovirus infections
• BK virus infections
• Cytomegalovirus infections
• Epstein-Barr virus infections
• Human herpesvirus-6 infections
• JC virus infections

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

T cells are highly effective in targeting cancer due to their sensitivity and specificity to antigens, but challenges like the rarity of tumor-reactive T cells and their unpredictable persistence limit their use in therapies.

Advancements in genetic modification technologies are being explored to enhance T cell responses to tumor antigens, with ongoing research focused on leveraging the diverse characteristics of T cells to improve the efficacy and safety of cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetically retargeting CD8+ lymphocyte subsets for cancer immunotherapy. Turtle, CJ., Riddell, SR.[2022]

Interleukin 7 (IL-7) significantly enhances the cytotoxic activity of virus-specific T cells in HIV-1-infected individuals, with the most effective results observed when IL-7 is added at the start of T cell activation cultures.

IL-7 acts independently of IL-2 to promote the maturation of precursor cytotoxic T lymphocytes (CTLs) into mature CTLs, suggesting its potential as a therapeutic agent to boost immune responses in AIDS and other viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 2-independent interleukin 7 activity enhances cytotoxic immune response of HIV-1-infected individuals. Carini, C., Essex, M.[2007]

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]

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]

Adoptive transfer of antigen-specific T cells shows promise for treating viral infections in immunosuppressed patients, but achieving effective T-cell therapy for cancer is more challenging due to issues like T-cell tolerance and impaired survival in the body.

Genetic modification of T cells before transfer may help overcome obstacles such as tumor evasion tactics and improve the effectiveness of T-cell therapies for both cancer and infectious diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of T cells for immunotherapy. Berger, C., Berger, M., Feng, J., et al.[2019]

Genetic modification of T cells to express receptors specific for tumor-associated antigens can redirect their function, enhancing their ability to target and eliminate tumor cells, which is crucial for treating common cancers.

Recent advances in gene design and cell production techniques have improved the clinical application of this adoptive immunotherapy, potentially leading to more effective treatments for patients with various types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic redirection of T cells for cancer therapy. Westwood, JA., Kershaw, MH.[2010]

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]

The study demonstrates that primary CD8+ T cells can be effectively reprogrammed to recognize HIV-1 by using RNA electroporation to transfer specific T-cell receptors, providing a safer alternative to retroviral transduction.

These reprogrammed T cells not only produced important cytokines but also efficiently targeted and killed HIV-1 infected cells, indicating their potential for therapeutic use in HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of HIV-1-specific T cells by electroporation of T-cell receptor RNA. Hofmann, C., Harrer, T., Kubesch, V., et al.[2008]

Genetic modification of T lymphocytes enhances their ability to recognize and attack tumor cells, which is crucial for improving cancer immunotherapy.

These modifications not only boost antitumor activity but also improve safety and allow for tracking of T cells using non-invasive imaging techniques, making them valuable for both research and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting tumours with genetically enhanced T lymphocytes. Sadelain, M., Rivière, I., Brentjens, R.[2021]

Cytotoxic T lymphocytes (CTLs) can be effectively generated from spleen cells of reovirus-infected mice when stimulated with reovirus-infected cells, demonstrating a targeted immune response.

The specificity of these CTLs is linked to the SI gene of the reovirus, which encodes the viral hemagglutinin and influences how the virus infects cells, particularly in the nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of cytolytic T lymphocytes after reovirus infection: role of S1 gene. Finberg, R., Weiner, HL., Fields, BN., et al.[2019]

Adoptive immunotherapy using virus-specific cytotoxic T cells (VSTs) has significantly advanced over the past 30 years, providing a promising method to restore immunity against viral infections after organ transplants, particularly for common pathogens like cytomegalovirus and Epstein-Barr virus.

Recent improvements in the manufacturing process of pathogen-specific T cells (pSTs) have made it possible to produce these cells more efficiently and even allow for off-the-shelf options, enhancing their availability for treating infections and related malignancies in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond. Papadopoulou, A., Alvanou, M., Karavalakis, G., et al.[2023]

Citations

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Virus-Specific T Cells for the Treatment of Systemic Infections ... This article provides a practical guide to VST therapy by reviewing manufacturing techniques, donor selection, and treatment indications.

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