Document Type
Article
Publication Date
8-2024
Abstract
Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received a single infusion of 1 of 4 escalating doses of a product containing 68.5% SARS-CoV-2-specific CD8+ CTLs/total cells. Symptom improvement and resolution in these patients was compared with an observational group of 18 patients lacking HLA-A∗02:01 who could receive standard of care. No dose-limiting toxicities were observed at any dosing level. Nasal swab polymerase chain reaction testing showed ≥88% and >99% viral elimination from baseline in all patients at 4 and 14 days after infusion, respectively. The CTLs did not interfere with the development of endogenous anti-SARS-CoV-2 humoral or cellular responses. T-cell receptor β analysis showed persistence of donor-derived SARS-CoV-2-specific CTLs through the end of the 6-month follow-up period. Interventional patients consistently reported symptomatic improvement 2 to 3 days after infusion, whereas improvement was more variable in observational patients. SARS-CoV-2-specific CTLs are a potentially feasible cellular therapy for COVID-19 illness. This trial was registered at www.clinicaltrials.gov as #NCT04765449.
Recommended Citation
Grosso, Dolores; Wagner, John L.; O'Connor, Allyson; Keck, Kaitlyn; Huang, Yanping; Wang, Zi-Xuan; Mehler, Hilary; Leiby, Benjamin; Flomenberg, Phyllis; Gergis, Usama; Nikbakht, Neda; Morris, Michael; Karp, Julie; Peedin, Alexis R.; and Flomenberg, Neal, "Safety and Feasibility of Third-Party Cytotoxic T Lymphocytes for High-Risk Patients With COVID-19" (2024). COVID-19 Papers, Posters, and Presentations. Paper 9.
https://jdc.jefferson.edu/covid-19/9
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Supplemental Tables, Figure, Methods, and References
Language
English
Comments
This article is the author's final published version in Blood Advances, Volume 8, Issue 15, 13 August 2024, Pages 4113 - 4124.
The published version is available at https://doi.org/10.1182/bloodadvances.2024013344. Copyright © 2024 by The American Society of Hematology.