A gB/CD3 bispecific BiTE antibody construct for targeting Human Cytomegalovirus-infected cells
| Autor: | Jochen Pendzialek, Markus Münz, Armin Ensser, Charlotte U. Brey, Julia Proff, Manfred Lehner, Johannes Brozy, Wolfgang Holter, Benjamin Salzer, Natascha Teufert |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Human cytomegalovirus CD3 Complex CD3 medicine.medical_treatment T cell viruses T-Lymphocytes Receptors Antigen T-Cell lcsh:Medicine Cytomegalovirus Biology Antibodies Viral Virus Replication Article 03 medical and health sciences 0302 clinical medicine Antigen Viral Envelope Proteins Antibody Specificity Antibodies Bispecific medicine Humans lcsh:Science Multidisciplinary lcsh:R Immunotherapy medicine.disease Virology Chimeric antigen receptor 030104 developmental biology Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Cytomegalovirus Infections biology.protein Cytokines lcsh:Q Antibody Protein Binding |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| ISSN: | 2045-2322 |
| Popis: | 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-γ 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. |
| Databáze: | OpenAIRE |
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