Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen-presenting cells.

Autor:	Ogando-Rivas E; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Castillo P; UF Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Florida, Gainesville, FL, USA., Yang C; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Trivedi V; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Zhang D; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Pohl-Guimarães F; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Liu R; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Barpujari A; UF Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Florida, Gainesville, FL, USA., Candelario KM; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Mendez-Gomez H; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA., Sayour EJ; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.; UF Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Florida, Gainesville, FL, USA., Mitchell DA; UF Brain Tumor Immunotherapy Program, Preston A. Wells Center for Brain Tumor Therapy, Lillian S. Wells Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2024 Jan 22; Vol. 32 (1), pp. 101192. Date of Electronic Publication: 2024 Jan 22 (Print Publication: 2024).
DOI:	10.1016/j.omtm.2024.101192
Abstrakt:	The COVID-19 pandemic has caused about seven million deaths worldwide. Preventative vaccines have been developed including Spike gp mRNA-based vaccines that provide protection to immunocompetent patients. However, patients with primary immunodeficiencies, patients with cancer, or hematopoietic stem cell transplant recipients are not able to mount robust immune responses against current vaccine approaches. We propose to target structural SARS-CoV-2 antigens (i.e., Spike gp, Membrane, Nucleocapsid, and Envelope) using circulating human antigen-presenting cells electroporated with full length SARS-CoV-2 structural protein-encoding mRNAs to activate and expand specific T cells. Based on the Th1-type cytokine and cytolytic enzyme secretion upon antigen rechallenge, we were able to generate SARS-CoV-2 specific T cells in up to 70% of unexposed unvaccinated healthy donors (HDs) after 3 subsequent stimulations and in 100% of recovered patients (RPs) after 2 stimulations. By means of SARS-CoV-2 specific TCRβ repertoire analysis, T cells specific to Spike gp-derived hypomutated regions were identified in HDs and RPs despite viral genomic evolution. Hence, we demonstrated that SARS-CoV-2 mRNA-loaded antigen-presenting cells are effective activating and expanding COVID19-specific T cells. This approach represents an alternative to patients who are not able to mount adaptive immune responses to current COVID-19 vaccines with potential protection across new variants that have conserved genetic regions. Competing Interests: The disclosures from D.A.M. are as follows: holds patented technologies that have been licensed or have exclusive options to license to Celldex Therapeutics, Annias, Immunomic Therapeutics, and iOncologi; receives research funding from Immunomic Therapeutics; he is also the cofounder of iOncologi, Inc., an immuno-oncology biotechnology company. The other authors have no conflicts of interest to disclose. E.O.R., V.T., F.P.G., C.Y., H.M.G, P.C, E.J.S, and D.A.M. have patents on mRNA technologies for COVID-19 and related to cellular therapy methods for viral vaccines. (© 2024 The Authors.)
Databáze:	MEDLINE
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