Generation of an oncolytic herpes simplex virus 1 expressing human MelanA

Journal article


Publication Details

Author(s): Boscheinen J, Thomann S, Knipe DM, Deluca N, Schuler-Thurner B, Gross S, Dörrie J, Schaft N, Bach C, Rohrhofer A, Werner-Klein M, Schmidt B, Schuster P
Journal: Frontiers in Immunology
Publication year: 2019
Volume: 10
Journal issue: JAN
ISSN: 1664-3224


Abstract

Robust anti-tumor immunity requires innate as well as adaptive immune responses. We have shown that plasmacytoid dendritic cells develop killer cell-like activity in melanoma cell cocultures after exposure to the infectious but replication-deficient herpes simplex virus 1 (HSV-1) d106S. To combine this innate effect with an enhanced adaptive immune response, the gene encoding human MelanA/MART-1 was inserted into HSV-1 d106S via homologous recombination to increase direct expression of this tumor antigen. Infection of Vero cells using this recombinant virus confirmed MelanA expression by Western blotting, flow cytometry, and immunofluorescence. HSV-1 d106S-MelanA induced expression of the transgene in fibroblast and melanoma cell lines not naturally expressing MelanA. Infection of a melanoma cell line with CRISPR-Cas9-mediated knockout of MelanA confirmed de novo expression of the transgene in the viral context. Dependent on MelanA expression, infected fibroblast and melanoma cell lines induced degranulation of HLA-matched MelanA-specific CD8+ T cells, followed by killing of infected cells. To study infection of immune cells, we exposed peripheral blood mononuclear cells and in vitro-differentiated macrophages to the parental HSV-1 d106S, resulting in expression of the transgene GFP in CD11c+ cells and macrophages. These data provide evidence that the application of MelanA-encoding HSV-1 d106S could enhance adaptive immune responses and re-direct MelanA-specific CD8+ T cells to tumor lesions, which have escaped adaptive immune responses via downregulation of their tumor antigen. Hence, HSV-1 d106S-MelanA harbors the potential to induce innate immune responses in conjunction with adaptive antitumor responses by CD8+ T cells, which should be evaluated in further studies.


FAU Authors / FAU Editors

Bach, Christian Dr. rer. nat.
Medizinische Klinik 5 - Hämatologie und Internistische Onkologie
Boscheinen, Jan Dr. med.
Anästhesiologische Klinik
Dörrie, Jan PD Dr.
Hautklinik
Thomann, Sabrina
Molekular-Immunologische Abteilung in der Medizinischen Klinik 3


External institutions with authors

Harvard University
Universität Regensburg
Universitätsklinikum Regensburg
University of Pittsburgh


How to cite

APA:
Boscheinen, J., Thomann, S., Knipe, D.M., Deluca, N., Schuler-Thurner, B., Gross, S.,... Schuster, P. (2019). Generation of an oncolytic herpes simplex virus 1 expressing human MelanA. Frontiers in Immunology, 10(JAN). https://dx.doi.org/10.3389/fimmu.2019.00002

MLA:
Boscheinen, Jan, et al. "Generation of an oncolytic herpes simplex virus 1 expressing human MelanA." Frontiers in Immunology 10.JAN (2019).

BibTeX: 

Last updated on 2019-23-05 at 10:23