Off-the-Shelf T Cells for SARS-CoV-2 Advance to Clinical Trial

The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of MPR’s conference coverage.

Allogeneic T cells with off-the-shelf potential showed preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), and are now being evaluated in a clinical trial.

The study findings were presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

Using peripheral blood mononuclear cells from patients who recovered from mild COVID-19 infection that did not require hospitalization, study researchers selectively stimulated and expanded memory T cells that had activity specifically against SARS-CoV-2 viral antigens.

These expanded virus-specific T cells were shown to be a mixture of CD4-positive and CD8-positive T cells that produced effector molecules, such as interferon gamma, tumor necrosis factor alpha, and granzyme B.

“This is the phenotype consistent with effective function and memory potential,” said study presenter Spyridoula Vasileiou, PhD, of the Center for Cell and Gene Therapy at the Baylor College of Medicine in Houston, Texas.

The virus-specific T cells also had in vitro cytotoxic activity, effectively lysing virus-expressing target cells while leaving noninfected cells intact.

These data demonstrate “the exquisite selectivity of these cells against the virus and [support] the safety for clinical use in high-risk COVID-19 patients,” Dr Vasileiou said.

Moderator Alisa Wolberg, PhD, University of North Carolina at Chapel Hill, commented, “The results signal a type of therapy that may be needed to treat patients who develop severe illness, even despite potential future vaccines.”

An open-label, proof-of-concept clinical trial (ClinicalTrials.gov Identifier: NCT04401410) is now underway in collaboration with AlloVir to evaluate the virus-specific T cells, also known as ALVR109. The trial is actively recruiting patients who are hospitalized with COVID-19 and have a high risk of needing a ventilator.

The trial design includes a phase 1 dose-escalation phase, which will evaluate 3 doses ranging from 10 to 14 million cells, and a randomization phase. For the randomization phase, patients will receive standard of care alone or standard of care plus a single infusion of virus-specific T cells.

Disclosures: Dr Vasileiou disclosed having consulted for and received funding from AlloVir. For a full list of disclosures, please refer to the presentation abstract.

Read more of MPR’s coverage of the ASH 2020 meeting by visiting the conference page.

Reference

Vasileiou S, Kuvalekar M, Workineh A, et al. Using allogeneic, off-the-shelf, Sars-Cov-2-specific T cells to treat high risk patients with COVID-19. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 612.

This article originally appeared on Cancer Therapy Advisor