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Antiviral T cells that are safe and effective as an off-the-shelf treatment for painful complications after stem cell transplantation

A phase II study led by researchers at the University of Texas MD Anderson Cancer Center found it to be specific to the BK virus (BKV). T cells From healthy donors, it was safe and effective as an off-the-shelf treatment for BKV-related hemorrhagic cystitis (BKV-HC), a common painful complication after allogeneic stem cell transplantation in patients with leukemia or lymphoma. .. Research today Journal of Clinical Oncology..

Injection of T cells targeting BKV resulted in a rapid response, with 67.7% of patients showing complete or partial improvement in symptoms after 14 days. This increased to 81.6% of patients 28 days after injection. No cases of Grade 3 or Grade 4 graft-versus-host disease (GVHD) or other injection-related toxicity occurred.

Dealing with debilitating complications caused by BKV

BKV-related hemorrhagic cystitis is a very painful condition that can cause serious morbidity in patients and can exacerbate cancer outcomes in the long run. Unfortunately, there is no effective treatment available. We have been urged to develop this treatment to provide better options for these patients, and this is a safe and effective treatment for MD Anderson patients based on these results. As emerged as. “

Katy Rezvani, MD, Ph.D. , Corresponding author, professor of stem cell transplantation and cell therapy

Rezvani explained that BKV is a human polyomavirus that infects most people in early childhood. BKV is normally suppressed by the immune system and remains inactive in cells that line the urethra, such as the kidneys, bladder, and ureter.

Allogeneic stem cell transplants from stem cell-matched donors require treatment of the patient to suppress the immune system and prevent rejection. However, this can also cause BKV to begin reproduction and cause severe cystitis, resulting in hospitalization for days or weeks. An antiviral drug called cidofovir has been used as a treatment, but it is highly toxic.

Development of antiviral T cell therapy

Recognizing that these viral infections can have a significant impact on patient recovery, Rezvani and her research team led the development of antiviral T cell therapy with the support of MDS and AML MoonShot®. .. Rapidly develop scientific discoveries into meaningful clinical advances that save the lives of patients.

Starting with blood samples taken from healthy donors, the research team isolated T cells, grew them, and varied. antigen Found in BKV. These cells are expanded in a Good Manufacturing Practices (GMP) laboratory under the guidance of Professor Elizabeth J. Spaul, a professor of stem cell transplantation and cell therapy. From each donor, the team can produce 20-50 doses of antiviral T cells and store them until needed, according to Rezvani.

In a previous study published in the New England Journal of Medicine, these researchers found that BKV-specific T cells are genetically similar, causing progressive multifocal leukoencephalopathy (PML), a rare and often fatal brain. It has been shown that the infection of JC virus, which is a polyomavirus, can be effectively treated.

BKV-specific T cells give positive test results

The current study enrolled a total of 59 MD Anderson patients experiencing BKV-HC after allogeneic stem cell transplantation. The median age of the patients was 47 years and they were treated for various hematological conditions. The most common is acute myeloid leukemia. 40.7% of the participants were women and 59.3% were men. Of the study participants, 55.9% (33) were Caucasian, 18.6% (11) were Hispanic, 15.3% (9) were African American, 6.8% (4) were Middle East, and 3.4% (2) were Asian. did.

Patients have the option of receiving a single injection of partially human leukocyte antigen (HLA) -matched T cells and an additional injection every two weeks as needed.

After the injection, the researchers did not observe any side effects that could be attributed to antiviral T cells. There were no infusion-related toxicity, decreased blood cell counts, or graft failure. Rezvani explained that several patients developed delayed cases of low-grade GVHD weeks and months after treatment and were within the expected rates of GVHD in these patients early after allogeneic stem cell transplantation.

The median time to partial response for patients was 14 days, and the median time to completion of response was 21 days. The estimated probability of achieving a complete response is almost 70% by day 45, indicating the continued activity of the injected cells. The response was persistent and no patient saw symptoms recur after a previously achieved response.

After studying the participants in the study, the researchers determined that the expansion of infused T was positively correlated with the patient’s response.

“I am very encouraged by the safety of this treatment and the rapid response seen in the majority of patients,” said Rezvani. “This approach is so safe that we were able to offer this treatment as an outpatient treatment as soon as the patient began to develop symptoms. This is life-changing for previously treated patients. did.”

In the future, researchers aim to validate these findings in multicenter studies and bring this treatment option to more patients in need.

A complete list of co-authors and their disclosures can be found in the complete treatise here. In addition to the Moonshot program, the study was supported by the National Institutes of Health (R01CA211044-05, CA0 16672).

Source:

Journal reference:

Olson, Z. , et al. (2021) Third-party BK virus-specific cytotoxic T lymphocyte therapy for hemorrhagic cystitis after allogeneic transplantation. Journal of Clinical Oncology. doi.org/10.1200/JCO.20.02608..

Antiviral T cells that are safe and effective as an off-the-shelf treatment for painful complications after stem cell transplantation

Source link Antiviral T cells that are safe and effective as an off-the-shelf treatment for painful complications after stem cell transplantation

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