A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells

Brey CU, Proff J, Teufert N, Salzer B, Brozy J, Muenz M, Pendzialek J, Enßer A, Holter W, Lehner M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 8

DOI: 10.1038/s41598-018-36055-2

Abstract

Bispecific T cell engager (BiTE) antibody constructs are successfully used as cancer therapeutics. We hypothesized that this treatment strategy could also be applicable for therapy of human cytomegalovirus (HCMV) infection, since HCMV-encoded proteins are abundantly expressed on the surface of infected cells. Here we show that a BiTE antibody construct directed against HCMV glycoprotein B (gB) and CD3 efficiently triggers T cells to secrete IFN-gamma and TNF upon co-culture with fibroblasts infected with HCMV strain AD169, Towne or Toledo. Titration of gB expression levels in non-infected cells confirmed that already low levels of gB are sufficient for efficient triggering of T cells in presence of the BiTE antibody construct. Comparison of redirecting T cells with the bispecific antibody versus a chimeric antigen receptor (CAR) based on the same scFv showed a similar sensitivity for gB expression. Although lysis of infected target cells was absent, the BiTE antibody construct inhibited HCMV replication by triggering cytokine production. Notably, even strongly diluted supernatants of the activated T cells efficiently blocked the replication of HCMV in infected primary fibroblasts. In summary, our data prove the functionality of the first BiTE antibody construct targeting an HCMV-encoded glycoprotein for inhibiting HCMV replication in infected cells.

Authors with CRIS profile

Natascha Teufert Institute of Clinical and Molecular Virology Armin Enßer Medizinische Fakultät

Involved external institutions

St. Anna Kinderkrebsforschung AT Austria (AT) Amgen GmbH DE Germany (DE)

How to cite

APA:

Brey, C.U., Proff, J., Teufert, N., Salzer, B., Brozy, J., Muenz, M.,... Lehner, M. (2018). A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells. Scientific Reports, 8. https://dx.doi.org/10.1038/s41598-018-36055-2

MLA:

Brey, Charlotte U., et al. "A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells." Scientific Reports 8 (2018).

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