Antiviral T cells protected, viable as off-the-shelf treatment for painful complication stem cells
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- Source: University of Texas M. D. Anderson Cancer Center
- Date: 02 May,2021
Infusion of T cells targeting BKV resulted in rapid responses, with 67.7% of patients seeing a complete or partial improvement in symptoms after 14 days. This increased to 81.6% of patients after 28 days post-infusion. No cases of grade 3 or grade 4 graft versus host disease (GVHD) or other infusion-related toxicities occurred.
Addressing a painful complication caused by BKV
BKV-associated hemorrhagic cystitis is an incredibly painful condition that causes significant morbidity in patients and can lead to worse cancer outcomes in the long term. Unfortunately, there are no effective treatments available. We were driven to develop this therapy to provide a better option for these patients, and this has emerged as a safe and effective therapy for patients at MD Anderson based on these results.”
Katy Rezvani, M.D., Ph.D., Corresponding Author, Professor of Stem Cell Transplantation and Cellular Therapy
BKV is a human polyomavirus acquired by most people in early youth, Rezvani explained. Held in check by the immune system, BKV typically stays dormant in the cells lining the urinary tract, including the kidney, liver, bladder and ureters.
Allogeneic stem cell transplants, where stem cells come from a matched donor, require patients to be given therapies to suppress the immune system and protect against rejection. However, this can also trigger the BKV to start reproducing and cause severe cystitis, which could lead to hospitalization for days or months. An antiviral called cidofovir was used as a treatment but is associated with significant toxicities.
Recognizing that these viral infections can profoundly impact patient healing, Rezvani and her research team directed the development of antiviral T-cell therapies with the support of the MDS and AML Moon Shot®, part of the institution’s Moon Shots Program®, a collaborative effort to quickly develop scientific discoveries into meaningful clinical improvements that save patients’ lives.
Starting with blood samples taken from healthy donors, the study team can isolate T cells and grow them to specifically recognize and target an assortment of antigens located on the BKV. These cells are expanded in the clinical good manufacturing practice (GMP) lab, under the direction of Elizabeth J. Shpall, M.D., professor of Stem Cell Transplantation and Cellular Therapy. From every donor, the team can fabricate anywhere from 20 to 50 doses of antiviral T cells, which can be stored until needed, Rezvani said.
In an earlier trial published in the New England Journal of Medicine, these researchers showed that BKV-specific T cells may effectively treat disease with the JC virus, a genetically similar polyomavirus which causes progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal brain infection.
BKV-specific T cells get positive results in trial
The current trial enrolled a total of 59 MD Anderson patients experiencing BKV-HC after an allogeneic stem cell transplant. Women accounted for 40.7% of participants and men for 59.3%.
Patients received a single infusion of partially human leukocyte antigen (HLA)-matched T cells, with the option to get additional infusions every 2 weeks, if necessary.
Following infusion, the researchers did not observe any side effects which were probably attributed to the antiviral T cells. Several patients developed delayed cases of low-grade GVHD in the weeks and months after therapy, which were well within the expected rates of GVHD for these patients early after allogeneic stem cell transplant, Rezvani explained.
The median time for patients to have a partial response was 14 days, and the median time to complete response was 21 days. The estimated probability of achieving a complete response was almost 70% by day 45, indicating continuous activity of the infused cells. Responses were durable and no patients saw their symptoms return after a formerly achieved response.
After analyzing participants on the trial, the researchers determined that expansion of the infused T was positively correlated with individual responses.
“We’re extremely encouraged by the safety of the treatment and the fast answers we have seen in the vast majority of patients,” Rezvani said. “Because this method is so safe, we have been able to provide this therapy as an outpatient procedure as soon as patients start developing symptoms. This has been life-changing for the patients we’ve been able to treat thus far.”
Ultimately, the researchers aim to validate these findings at a multi-institutional research and bring this treatment option to many more patients in need.
A complete list of cooperating authors and their disclosures are available with the full paper here. In addition to the Moon Shots Program, the study was supported by the National Institutes of Health (R01CA211044-05, CA016672).
Olson, Z., et al. (2021) Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation. Journal of Clinical Oncology. doi.org/10.1200/JCO.20.02608.