Envelope-Specific Adaptive Immunity following Transplantation of Hematopoietic Stem Cells Modified with VSV-G Lentivirus.

Autor:	Rust BJ; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA., Becker PS; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA.; Department of Medicine, University of Washington, Seattle, WA 98195, USA., Chandrasekaran D; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA., Kubek SP; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA., Peterson CW; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA.; Department of Medicine, University of Washington, Seattle, WA 98195, USA., Adair JE; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA.; Department of Medicine, University of Washington, Seattle, WA 98195, USA., Kiem HP; Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 91911, USA.; Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2020 Oct 10; Vol. 19, pp. 438-446. Date of Electronic Publication: 2020 Oct 10 (Print Publication: 2020).
DOI:	10.1016/j.omtm.2020.10.002
Abstrakt:	Current approaches for hematopoietic stem cell gene therapy typically involve lentiviral gene transfer in tandem with a conditioning regimen to aid stem cell engraftment. Although many pseudotyped envelopes have the capacity to be immunogenic due to their viral origins, thus far immune responses against the most common envelope, vesicular stomatitis virus glycoprotein G (VSV-G), have not been reported in hematopoietic stem cell gene therapy trials. Herein, we report on two Fanconi anemia patients who underwent autologous transplantation of a lineage-depleted, gene-modified hematopoietic stem cell product without conditioning. We observed the induction of robust VSV-G-specific immunity, consistent with low/undetectable gene marking in both patients. Upon further interrogation, adaptive immune mechanisms directed against VSV-G were detected following transplantation in both patients, including increased VSV-G-specific T cell responses, anti-VSV-G immunoglobulin G (IgG), and cytotoxic responses that can specifically kill VSV-G-expressing target cell lines. A proportion of healthy controls also displayed preexisting VSV-G-specific CD4 + and CD8 + T cell responses, as well as VSV-G-specific IgG. Taken together, these data show that VSV-G-pseudotyped lentiviral vectors have the ability to elicit interfering adaptive immune responses in the context of certain hematopoietic stem cell transplantation settings. (© 2020 The Authors.)
Databáze:	MEDLINE
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